Towards the quantification of perioperative cardiovascular risk in the African context: A sub-analysis of the South African Surgical Outcomes Study and the African Surgical Outcomes Study.

BACKGROUND: The burden of cardiovascular disease in patients requiring non-cardiac surgery in Africa is not known. These patients are at increased risk for postoperative cardiovascular complications. OBJECTIVES: In this sub-study, to use data on comorbidities and surgical outcomes from two large observational studies, the South African Surgical Outcomes Study (SASOS) and the African Surgical Outcomes Study (ASOS), to investigate the prevalence of cardiovascular disease in elective surgical patients and the risk of postoperative cardiovascular complications in this population. METHODS: SASOS and ASOS were both prospective, observational cohort studies that collected data over 1 week in each participating centre. The primary outcome was in-hospital postoperative complications, which included prespecified and defined cardiovascular complications. We defined the cardiovascular disease burden of patients aged ≥45 years presenting for surgery (main objective), determined the relative risk of developing postoperative cardiovascular complications (secondary objective) and assessed the utility of the Revised Cardiac Risk Index (RCRI) for preoperative cardiovascular risk stratification of elective, non-cardiac surgical patients in Africa (third objective). RESULTS: The primary outcome analysis of 3 045 patients showed that patients with major cardiac complications were significantly older, with a higher prevalence of hypertension, coronary artery disease or congestive cardiac failure, and had undergone major surgery. In-hospital mortality for the cohort was 1.2%. CONCLUSIONS: The substantial burden of cardiovascular disease in patients presenting for non-cardiac surgery in Africa is shown in the principal findings of this study. The RCRI has moderate discrimination for major cardiac complications and major adverse cardiac events in African patients undergoing non-cardiac surgery.

Hybrid capture 2 and cobas® 4800: Comparison of performance of two clinically validated tests for human papillomavirus primary screening of cervical cancer.

OBJECTIVE: To compare, in a primary human papillomavirus screening setting, two different validated human papillomavirus tests, considering their analytical and clinical screening performances. METHODS: In Tuscany, a human papillomavirus screening program was implemented in 2013. Hybrid capture 2 (Qiagen) was used for testing until May 2016, when it was replaced by the cobas® 4800 human papillomavirus test (Cobas; Roche). We evaluated the performance of Hybrid capture 2 and Cobas on: the same screening population in two different periods (before and after changing to Cobas); the same Hybrid capture 2-positive consecutive samples. Discordant samples (Hybrid capture 2-positive/Cobas negative) were typed on the L1 gene (reverse line blot, AB Analitica) and E6/E7 genes (BD Onclarity assay). RESULTS: In the considered time period (n = 37,775), human papillomavirus positivity was 9.8% and 7.4%, respectively, for Hybrid capture 2 and Cobas (p < 0.0001). At immediate colposcopy, the cervical intraepithelial neoplasia, grade 2 positive predictive value was, respectively, 23.8% and 34% (p < 0.001). At one-year recall, human papillomavirus persistence was, respectively, 40.6% and 62.2% (p < 0.0001). Of Hybrid capture 2-positive re-tested samples (n = 620), 32.4% were Cobas negative. Of discordant samples typed on L1, 7% were positive for the 12 high-risk human papillomavirus. Of the samples found to be negative for the 12 high-risk human papillomavirus types on L1, 14.5% were positive on E6/E7 typing. Among the discordant samples, the only two cervical intraepithelial neoplasia (CIN) grade 3 lesions were non-high-risk human papillomavirus positive on both L1 and E6/E7 typing. CONCLUSION: At baseline, Hybrid capture 2 showed greater human papillomavirus positivity and a lower CIN2+ positive predictive value than Cobas, which was more specific than Hybrid capture 2 in detection of high-risk human papillomavirus: 80% of discordant samples were confirmed as high-risk human papillomavirus negative. This higher analytical specificity determined the non-identification of two CIN3 lesions.

The African Surgical OutcomeS-2 (ASOS-2) Pilot Trial, a mixed-methods implementation study

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. The working hypothesis is that patients die as a result of failure to rescue following complications in the postoperative period. The African Surgical OutcomeS-2 (ASOS-2) Trial plans to test the efficacy of increased postoperative surveillance in high risk patients for decreasing perioperative morbidity and mortality. This pilot trial aimed i) to evaluate the adequacy of data produced by the data collection strategies of the ASOS-2 Trial, ii) to evaluate the fidelity of implementation of the increased postoperative surveillance intervention, and iii) to understand the acceptability, appropriateness and feasibility of the intervention and the trial processes. Methods: The ASOS-2 Pilot Trial was a mixed-methods (quantitative-qualitative) implementation study focusing on the intervention arm of the proposed ASOS-2 Trial. The intervention is increased postoperative surveillance for high-risk surgical patients. The intervention protocol was implemented at all sites for a seven-day period. A post pilot trial survey was used to collect data on the implementation outcomes. Results: 803 patients were recruited from 16 hospitals in eight African countries. The sampling and data collection strategies provided 98% complete data collection. Seventy-three percent of respondents believed that they truly provided increased postoperative surveillance to high risk patients. In reality 83/125 (66%) of high-risk patients received some form of increased postoperative surveillance. However, the individual components of the increased postoperative surveillance intervention were implemented in less than 50% of high-risk patients (excepting increasing nursing observations). The components most frequently unavailable were the ability to provide care in a higher care ward (32.1%) and assigning the patient to a bed in view of the nurses' station (28.4%). Failure to comply with available components of the intervention ranged from 27.5% to 54.3%. The post pilot survey had a response rate of 30/40 (75%). In Likert scale questions about acceptability, appropriateness, and feasibility of the ASOS-2 intervention, 63% to 87% of respondents indicated agreement. Respondents reported barriers related to resources, trial processes, teamwork and communication as reasons for disagreement. Conclusions: The proposed ASOS-2 Trial appears to be appropriate, acceptable and feasible in Africa. This pilot trial provides support for the proposed ASOS-2 Trial. It emphasises the need for establishing trial site teams which address the needs of all stakeholders during the trial. A concerted effort must be made to help participating hospitals to increase compliance with all the components of the proposed intervention of 'increased postoperative surveillance' during the ASOS-2 Trial

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

Codon 72 polymorphism of p53 and HPV type 16 E6 variants as risk factors for patients with squamous epithelial lesion of the uterine cervix.

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene in association with human papillomavirus (HPV) 16 E6 variants has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. The association of p53 codon 72 polymorphism alone and in combination with specific HPV 16 E6 variants with risk of developing squamous intraepithelial cervical lesion has been investigated in low and high-grade squamous intraepithelial lesions and in HPV-negative controls from an Italian population. The data obtained showed statistically significant different distribution of p53 genotypes between healthy controls and precursor lesions, with the p53 arginine homozygous increased in high-grade squamous intraepithelial lesions. The T350G HPV 16 variant was the most frequent variant observed in the analyzed group of Italian women, showing a slight decreasing with the severity of the lesion. At the same time, the number of the prototype T350 slightly increased with the severity of the cytological lesions. In conclusion, p53 arginine homozygous was found to be increased in high-grade lesions, supporting the results of previous investigations indicating that HPV-positive patients with p53 Arg/Arg have an increased risk of developing pre-cancerous lesions. In addition, T350G HPV 16 variant was over-represented in p53 Arg homozygous women with cervical lesions. When p53 genotype and HPV 16 variants are considered together, no difference emerges between cases and controls so is not possible to assess that the oncogenic effect of HPV 16 T350G variant may be influenced by the p53 genotype.

Comparison of clinical performance of Abbott RealTime High Risk HPV test with that of hybrid capture 2 assay in a screening setting.

Randomized trials have produced sound evidence about the efficacy of screening with human papillomavirus (HPV) DNA tests in reducing cervical cancer incidence and mortality. We evaluated the clinical performance and reproducibility of the Abbott RealTime High Risk (HR) HPV test compared with that of the HR hybrid capture 2 (HC2) assay as assessed by a noninferiority score test. A random sample of 998 cervical specimens (914 specimens of cervical intraepithelial neoplasia less severe than grade 2 [

The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600).

BACKGROUND: In Italy, cervical cancer screening programmes actively invite women aged 25-64 years. Programmes are hindered by low participation. METHODS: A sample of non-responder women aged 35-64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home. RESULTS: Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24-2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61-1.50), a prevalently rural area. CONCLUSIONS: Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.

Antidiarrhoeal activity of the methanol stem-bark extract of Annona senegalensis Pers. (Annonaceae).

AIM OF THE STUDY: To investigate the antidiarrhoeal properties of the stem-bark extract of Annona senegalensis, using both in vivo and in vitro models. MATERIALS AND METHODS: Swiss albino mice were used to investigate the acute oral toxicity of the extract. The extract was administered orally to mice fed with charcoal meal in order to investigate intestinal transit time. The effect of the extract on contraction of isolated rabbit jejunum and the responses of the tissue to acetylcholine and histamine were also investigated. RESULTS: The extract was safe at doses up to 5000 mg/kg. The extract at the dose of 10mg/kg significantly (p<0.05) decreased intestinal transit time at concentrations of 0.2-3.2 mg/ml, the extract attenuated spontaneous contractions of the isolated rabbit jejunum, and those induced by acetylcholine in a concentration-dependent fashion. CONCLUSION: The extract decreased intestinal transit time by attenuating the spontaneous contractions of the intestine, thus the study provided a scientific basis for the use of Annona senegalensis stem bark extract in the treatment of diarrhoea.

Technical evaluation of the new thin layer device CellSlide (Menarini Diagnostics).

The CellSlide Processor (Menarini Diagnostics) is an automatic computer-controlled instrument, designed to prepare standardized, thin-layer cytological preparations using a filtration process. In this report, this new processor has been tested in a multicentric investigation, designed to evaluate cell recovery, cellular morphology and possible time saved in reading the slide. The results of this study show that the CellSlide processing system is suitable for use in the preparation of liquid-based gynaecology samples. Furthermore, the high-quality smear produced by the CellSlide decreases the reading time by approximately 20-25%.

Association of human papillomavirus with prostate cancer: analysis of a consecutive series of prostate biopsies.

The study purpose was to investigate the association of human papillomavirus (HPV) infection with prostate cancer. The presence and type of HPV DNA were investigated by polymerase chain reaction in the preservation fluid of 60 consecutive prostate core biopsies (29 benign, 31 malignant). The material was inadequate (no DNA found at beta-globin testing) in four benign and five cancer biopsies. HPV DNA was found in 17 of 26 (65.3%) cancer and 12 of 25 (48.0%) benign biopsies (chi2 = 0.94, p = 0.33). High-risk HPV type positivity was observed in 14 of 26 (53.8%) cancer and in five of 25 (20.0%) benign biopsies (chi2 = 4.38, p = 0.03). Twenty-three of 29 cases were positive at L1 region testing with MY09/11 primers; testing with primers directed to the E6/E7 region revealed six further HPV-positive cases (four cancer, two benign). The presence of HPV in prostate tissue suggests a possible reservoir for sexual transmission of types with oncogenic potential. Our findings also suggest a possible role of high-risk HPV infection in the etiology of prostate cancer and encourage further research into this issue.

Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood.

OBJECTIVES: Screening by faecal occult blood testing (FOBT) is effective in decreasing mortality and incidence of colorectal cancer (CRC). Immunochemical tests have proved to be more cost effective than guaiac FOBTs. The latex agglutination test (LAT) has the advantage of being a fully automated, quantitative test. The aim of this study is to interpret the overall experience with LAT according to different positivity thresholds. SETTING: A population based screening programme is currently running involving subjects aged 50-70, invited every 2 years to have an FOBT. LAT is the standard screening test and has a positivity threshold for further diagnostic tests of 100 ng haemoglobin/ml of sample solution. METHODS: Positivity rates, detection rates for CRC high risk adenomas, and positive predictive values for CRC, high risk adenomas, and low risk adenomas were calculated for several positivity thresholds. RESULTS: 19,132 attendances at screening were recorded (11,774 at first screening, 7358 at subsequent screenings). Progressively increasing the positivity threshold from 100 to 200 ng/ml showed (a) a decrease in positivity rate; (b) a decrease in detection rates for CRC or high risk adenomas; (c) an increase in positive predictive values for cancer; (d) an increase in positive predictive value for high risk adenomas. CONCLUSIONS: Increasing the positivity threshold of the LAT reduces recall rate and improves positive predictive value for cancer or high risk adenomas but substantially decreases the detection rate of CRC and high risk adenomas. For this reason increasing the positivity cut off for LATs is not advisable. On the other hand decreasing the positivity threshold would increase recall rate and sensitivity of screening. Careful evaluation of sensitivity of the quantitative results of the LAT for interval cancers is needed to definitively assess the optimal positivity threshold for LATs in population based screening programmes.

-344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension.

Most patients with low renin essential hypertension are not qualitatively different from patients with idiopathic hyperaldosteronism, as in both conditions aldosterone secretion is not appropriately reduced. The aim of the study was to investigate allele and genotype frequencies of the -344C/T polymorphism, located in the promoter region of the aldosterone synthase gene, in 83 patients with idiopathic low renin hypertension characterized by an increased aldosterone to renin ratio, including both patients with low renin essential hypertension (n=53) and subjects with idiopathic hyperaldosteronism (n=30), compared with 78 patients with normal to high renin essential hypertension and 126 normotensive control subjects. The relationship of -344C/T genotypes to basal and postcaptopril plasma aldosterone/plasma renin activity ratio was also examined in the entire hypertensive population. An increased frequency of the T allele and a relative excess of TT homozygosity over CC homozygosity were found in patients with idiopathic low renin hypertension in comparison with both normal to high renin hypertensives and normotensive controls. A higher post-captopril aldosterone to renin ratio was found in the hypertensives with TT genotype than in those with CC genotype, and TT+TC genotypes were associated with a smaller decrease in the aldosterone-to-renin ratio elicited by captopril administration. The present study suggests that the -344C/T polymorphism, or a functional variant in linkage disequilibrium with it, may play a role in the abnormal regulation of aldosterone secretion in idiopathic low renin hypertension.

Colorectal cancer screening by fecal occult blood testing: results of a population-based experience.

AIMS AND BACKGROUND: The study evaluated the results of an experimental screening protocol for colorectal cancer by fecal occult blood testing in a municipality of the Province of Florence. METHODS: A total of 15,235 subjects aged 50-70 years were invited to perform a 1-day immunochemical fecal occult blood testing without any dietary restrictions. All eligible subjects were sent a personal invitation letter, followed by a postal reminder to non-responders. Subjects with a negative stool test were advised to repeat screening after 2 years. Subjects with a positive screening test were invited to undergo full colonoscopy or a combination of left colonoscopy and a double contrast barium enema. RESULTS: A total of 6,418 subjects performed the screening test, with an overall compliance of 42.1%. A total of 268 compliers had positive test results. The positivity rate was 4.2%. Detection rate for cancer and for adenomas was 5.1% and 11.6%, respectively. The positive predictive value was 14.3% for cancer and 32.5% for adenoma. A higher compliance was recorded in subjects born in the province of Florence or living in the centre of the town, in married subjects, and in women. The best results in compliance were associated with the direct distribution of fecal occult blood testing kits by general practitioners to their outpatients. CONCLUSIONS: The study provides useful information about the efficiency and feasibility of a screening program for colorectal cancer using fecal occult blood testing. Compliance results confirm the importance of GP involvement in oncological screening.

Screening for colorectal cancer by faecal occult blood test: comparison of immunochemical tests.

OBJECTIVE: To compare two immunochemical faecal occult blood tests based on reversed passive haemagglutination (RPHA) or latex agglutination (Hdia) in a population based screening setting. METHOD: Hdia was interpreted according to three positivity thresholds: 100, 150, or 200 ng of haemoglobin/mg of specimen solution. A total of 5844 subjects were recruited into the study, from 17432 invited subjects aged 50-70. RESULTS: Positivity rates were 3.3% for RPHA, Hdia100 3.5%, Hdia150 2.5%, Hdia200 2.0%. Among subjects complying with the diagnostic work up, colorectal cancer (CRC) was detected in 19 subjects (17 RPHA positive, 16 Hdia100 positive, 15 Hdia150 positive, 14 Hdia200 positive) and high risk adenoma/s in 41 subjects (28 RPHA positive, 32 Hdia100 positive, 29 Hdia150 positive, 25 Hdia200 positive). The prevalence of screen positive CRC in the population was for RPHA 2.9 per thousand, Hdia100 2.7 per thousand, Hdia150 2.6 per thousand, Hdia200 2.4 per thousand. The prevalence of screen positive high risk adenomas in the population was for RPHA 4.8 per thousand, Hdia100 5.5 per thousand, Hdia150 5.0 per thousand, Hdia200 4.3 per thousand. CONCLUSION: Hdia100 was as sensitive as RPHA for cancer and high risk adenomas. As Hdia is less technically complex than RPHA, it is a valid alternative to the latter, provided that full automation of the development procedure is available. Increasing the positivity threshold of Hdia up to 150 or 200 ng of haemoglobin/mg of specimen solution is not advisable as the increase in specificity is too small to justify the corresponding decrease in the detection of screen positive cancers in the population.

The use of prosthesis in abdominal and thoracic wall defect, 15 year experience: evaluation of tissue reactions and complications.

Synthetic prosthesis (Polypropylene, Dacron and expanded Polyterafluoroethylene) is now widely used in abdominal and thoracic wall reconstructive surgery. Many surgeons have reported great success with various types of prosthetic implants but tissue reactions and other complications have never been well defined. The aim of this study was to determine which molecules react upon tissue contact, which synthetic materials result in less complications and whether some non-specialized prosthetics are correlated with certain types of complications. We studied 54 patients from 1982-1997 who had each been re-operated on for prosthetic complications. Our clinical data was then compared to data collected from animal models. Twenty-one pigs received one or more prosthetic implants: 14 of these pigs received their implants with a "proper surgical technique" while 8 underwent "improper surgical technique". The results from both the clinical and animal study were significantly similar. From a microscopic point of view, we can conclude that different tissues react in the same way with the same or similar types of prostheses. The reactions begin to differ when the thickness and rigidity of the material is considered. A PTFE-polyporpylene combination (Composix Mesh) seems to be the most effective solution, especially in abdominal defect repair which involves peritoneal organ contact. We would also like to emphasize that prosthetic complications can be quite serious and this type of procedure should only be performed by experienced and qualified surgeons.

Increased plasma levels of platelet-derived growth factor (PDGF-BB + PDGF-AB) in patients with never-treated mild essential hypertension.

Platelet-derived growth factor (PDGF) could play a role in both vascular hypertrophy and atherosclerotic disease associated with hypertension. To assess whether plasma PDGF level is increased in mild essential hypertension, we measured plasma PDGF concentration in 25 never-treated patients with uncomplicated mild essential hypertension and in 22 normotensive healthy subjects. To evaluate the contribution of platelets to plasma PDGF in the two groups, we also measured plasma beta-thromboglobulin (BTG). Measurement of PDGF was carried out through an enzyme-linked immunoadsorbent assay, which detects two PDGF dimers, namely PDGF-BB and PDGF-AB. Both plasma PDGF and BTG were higher in the hypertensive than in the normotensive subjects. The ratio of PDGF to BTG was similar in the two groups. Plasma PDGF was weakly correlated with plasma BTG in the normotensive subjects, whereas this relationship was lost in the hypertensive patients. Our results suggest that the increase in plasma PDGF (PDGF-AB + PDGF-BB) in never-treated essential hypertension is mainly due to platelet activation. The increased circulating level of PDGF could play a role in the vascular structural changes associated with hypertension.

Acute effects of intravenous sodium chloride load on calcium metabolism and on parathyroid function in patients with primary aldosteronism compared with subjects with essential hypertension.

To elucidate the mechanisms involved in increased parathyroid function in primary aldosteronism (PA), we evaluated the effects of an intravenous NaCl load on Ca metabolism and plasma level of intact parathyroid hormone (PTH) in patients with PA compared with that in patients with essential hypertension (EH). Sixteen PA patients and 16 EH patients who were well matched for age, gender, body mass index, renal function, and systolic (SBP) and diastolic blood pressure (DBP) were examined. In each subject, after 6 days of a controlled intake of Na, K, and Ca, isotonic saline was infused at a rate of 500 mL/h for 4 h. At baseline, in spite of similar BP values and urinary Na excretion (U[Na]V), urinary excretion of Ca (U[Ca]V) and PTH were higher in the PA group than in the EH group. In both groups, the NaCl load caused a decrease of serum ionized Ca (Ca2+) and an increase in PTH, U(Na)V, and U(Ca)V. However, these changes were significantly greater in the PA group. The increased baseline U(Ca)V in PA could be due to reduced reabsorption of sodium in aldosterone insensitive tubular sites, as a result of the "escape phenomenon." The increased U(Ca)V may explain the higher basal PTH in PA patients, which is needed for maintaining a normal Ca2+. The greater changes in the Ca2+/PTH profile elicited by the saline load in PA patients are apparently due to a higher calciuretic response following a more exaggerated natriuresis in PA.

Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.

OBJECTIVE: To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-). METHODS: Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests. RESULTS: 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased. CONCLUSIONS: Our data confirm that screening by RPHA is more cost effective than by Hemoccult.