Early Diagnosis Program Research Articles

Cutaneous melanoma in octogenarians: a single-institution review

To identify the prognostic factors and assess the outcome of a group of octogenarian patients who were diagnosed with cutaneous melanoma (CM) in the Department of Dermatology of the "M. Bufalini" Hospital, Cesena, Italy from 1996 to 2013. From the 1136 consecutive patients in our database, we selected 82 patients (7.2%) diagnosed with CM at age 80 or older. Their major clinical and histopathologic parameters were extracted and matched with those of the residual 1054 younger patients. Comparing our 82 patients with the group of 1054 patients with CM diagnosed in the same period, but at a younger age, we found that: 1) there was no significant difference regarding the patient's gender; 2) CM diagnosed in octogenarians was more frequently located on the head and neck (24.4% vs. 12.8%), and lower extremities (24.4% vs. 14.4%) (P=0.0001); 3) early diagnosis of CM (T1) was less frequent in octogenarians (31.7% vs. 62.6%), intermedium thickness CM (T2) was nearly the same in the 2 groups (15.8% vs. 16.5%), while diagnosis in category T3/T4 (42.6% vs. 21.0%) were significantly greater in octogenarians (P=0.0001); 4) ulceration was detected more frequently in octogenarians (18.3% vs. 10.7%) but the difference was not statistically significant. After a follow-up period of a median 58 months, 52 octogenarians (63.4%) were still alive and free from disease. Thirty of them (36.6%) had died, 14 (17.1%) of which because of melanoma. On the contrary, among the younger patients, 840 (81.6%) were alive, 132 (12.5%) died for melanoma and 75 (7.1%) for other causes. In our octogenarians, death for CM was not related to the old age but to the delayed diagnosis of cancer. Our results suggest that continuing educational programs for early diagnosis of CM should specifically include this segment of population.

Acromegalia y tumores asociados: ¿qué debemos saber los gastroenterólogos?

Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients.

Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico.

The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease.

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Hospital admissions from a pediatric HIV care and treatment program in Malawi.

BackgroundThe scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery.MethodsWe conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children’s Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions.ResultsOf 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12–62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common.ConclusionsIllness requiring hospitalization is common in HIV-infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients.

Is integrating sickle cell disease and HIV screening logical?

Is integrating sickle cell disease and HIV screening logical?

Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study.

Sickle cell disease contributes substantially to mortality in children younger than 5 years in sub-Saharan Africa. In Uganda, 20,000 babies per year are thought to be born with sickle cell disease, but accurate data are not available. We did the cross-sectional Uganda Sickle Surveillance Study to assess the burden of disease. The primary objective of the study was to calculate prevalence of sickle cell trait and disease. We obtained punch samples from dried blood spots routinely collected from HIV-exposed infants in ten regions and 112 districts across Uganda for the national Early Infant Diagnosis programme. Haemoglobin electrophoresis by isoelectric focusing was done on all samples to identify those from babies with sickle trait or disease. Between February, 2014, and March, 2015, 99,243 dried blood spots were analysed and results were available for 97,631. The overall number of children with sickle cell trait was 12,979 (13·3%) and with disease was 716 (0·7%). Sickle cell numbers ranged from 631 (4·6%) for trait and 23 (0·2%) for disease of 13,649 in the South Western region to 1306 (19·8%) for trait and 96 (1·5%) for disease of 6581 in the East Central region. Sickle cell trait was seen in all districts. The lowest prevalence was less than 3·0% in two districts. Eight districts had prevalence greater than 20·0%, with the highest being 23·9%. Sickle cell disease was less common in children older than 12 months or who were HIV positive, which is consistent with comorbidity and early mortality. Prevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening. Cincinnati Children's Research Foundation.

Diagnóstico precoz de la infección por el virus de la inmunodeficiencia humana-1 en niños: programa de prevención de la transmisión maternoinfantil en Guinea Ecuatorial

BackgroundGreat efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. MethodsA prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. ResultsSixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). ConclusionsThe PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.

The Burden of HIV Associated Drug Resistance Mutations in an Early Infant Diagnosis Program: A Glance through the Paediatric Window of Zimbabwe

There is paucity of information on the prevalence of human immunodeficiency virus type 1 drug-resistance mutations in infants infected despite prevention of mother to child transmission in Zimbabwe. This study examined 32 dried blood spot specimens from HIV- 1 C infected infants born alive to women receiving antiretroviral therapy, who were part of the WHO/ResNet early infant diagnosis program between January 2010 and January 2011. The objective was to determine the patterns and levels of HIV drug resistance and inform on policy formulation. Overall HIV prevalence of the infants in the retrospect study period was 2.4% (32/1356). Half of the samples (16/32) analyzed had HIV associated drug resistance mutations, however excluding polymorphic mutations the HIV drug resistant mutations were 25% (8/32). Frequencies of the mutations were (E138A, n=6; G190A, n=1; M230ML, n=1; K103KN, n=1; Y181C, n=5; V90VI, n=1; E138G, n=1; E138EA, n=1). One patient had two mutations the K103KN and the Y181C. Of the sixteen patients with HIV drug resistance mutations, 5 had nevirapine only resistance, none had lamivudine resistance and 8 had both etravirine and rilpivirine resistance, 2 had both nevirapine, efavirenz and 1 had rilpivirine only. The study shows an apparent non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance predominance and suggests a judicious use of NNRTI regimens and a prudent strategy to minimize the selection of drug resistance mutations.

Change in the prevalence of metabolic syndrome in a population of medical students: 6-year follow-up.

Students of a university hospital were assessed in 2007 and later in 2013 to determine the prevalence of metabolic syndrome. Statistical analysis was done with SPSS version 17.0.A total of 213 students were evaluated in both 2007 and 2013 (48.3 % women and 51.7 % men). The diagnosis of overweight and obesity increased from 24.9 to 37.1 % (p < 0.05), central obesity from 17.8 to 28.6 % (p < 0.05), and prevalence of metabolic syndrome from 9.8 to 14.5 % (p ≥ 0.05); up to 20 % in male gender. It is important to implement programs for early diagnosis of metabolic syndrome.

PMS136 - Effectiveness of A Referral Program for Early Arthritis Diagnosis At Primary Care Centers in Portugal - Preliminary Results from the Siara Study

PMS136 - Effectiveness of A Referral Program for Early Arthritis Diagnosis At Primary Care Centers in Portugal - Preliminary Results from the Siara Study

Implementation and Operational Research: Expedited Results Delivery Systems Using GPRS Technology Significantly Reduce Early Infant Diagnosis Test Turnaround Times.

The objective of this study was to quantify the impact of a new technology to communicate the results of an infant HIV diagnostic test on test turnaround time and to quantify the association between late delivery of test results and patient loss to follow-up. We used data collected during a pilot implementation of Global Package Radio Service (GPRS) printers for communicating results in the early infant diagnosis program in Mozambique from 2008 through 2010. Our dataset comprised 1757 patient records, of which 767 were from before implementation and 990 from after implementation of expedited results delivery system. We used multivariate logistic regression model to determine the association between late result delivery (more than 30 days between sample collection and result delivery to the health facility) and the probability of result collection by the infant's caregiver. We used a sample selection model to determine the association between late result delivery to the facility and further delay in collection of results by the caregiver. The mean test turnaround time reduced from 68.13 to 41.05 days post-expedited results delivery system. Caregivers collected only 665 (37.8%) of the 1757 results. After controlling for confounders, the late delivery of results was associated with a reduction of approximately 18% (0.44 vs. 0.36; P < 0.01) in the probability of results collected by the caregivers (odds ratio = 0.67, P < 0.05). Late delivery of results was also associated with a further average increase in 20.91 days of delay in collection of results (P < 0.01). Early infant diagnosis program managers should further evaluate the cost-effectiveness of operational interventions (eg, GPRS printers) that reduce delays.

Early Diagnosis of Multiple Myeloma - Project CRAB of Czech Myeloma Group(CMG)

Introduction: Multiple myeloma is one of the most frequent hematological malignancies. The prognosis of patients has substantially improved due to new treatment options. However, the early diagnosis is still a crucial factor for prognosis. First symptoms of myeloma are different and mostly unspecific - therefore many patients are diagnosed late with serious organ and/or tissue damage. Czech Myeloma Group initiated the program for early diagnosis of MM in 2007. Program (named due to educational reasons„CRAB“) was focused on general practitioners (GPs) and key specialists responsible for recognizing the symptoms related to MM (neurology, orthopedics, nephrology). We present results of the final analysis. Methods: a/ telephonic survey for healthcare professionals, b/ written information for primary care providers, c/ brochures containing definition of clinical symptoms and recommended diagnostic methods, d/ patient questionnaire, e/ presentations at medical meetings in Czech republic, f/ presentation in non-hematological medical journals, g/ e-learning. Primary objectives were: 1) decrease risk of late diagnosis ( > 3 month after first symptoms of myeloma) from 50% to 30% , 2) reduction of irreversible deterioration at the time of diagnosis from 20% to <10%. Secondary objectives were: 3) improve knowledge of the first-contact care providers about the initial symptoms of multiple myeloma 4) inform them about diagnostic methods applicable in first-contact care 5) inform them about new treatment modalities and improving prognosis of myeloma patiens. Planned project duration was 7 years (2007-2013). The first interim analysis was done in 2010. Results: 76,4% patients was diagnosed < 3 month after first contact with healthcare professionals according to the second analysis in 2013. Probability of early diagnosed patients increased from 53,5% in 2007 to 68,8%, ,i.e. by 29% , in 2013 However, incidence of the osteolytic lesions and renal failure at time of diagnosis remained similar. Conclusion: The 7-year project leads to the increase of early diagnosis of MM by almost one third. Long-term analysis will show whether better knowledge of medical society about myeloma is transient (just during information campaign) or permanent. Project was supported by Czech Myeloma Group and Jansen-Cillag. Disclosures Hajek: Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Honoraria.

A novel approach to study evolution of drug resistance and optimum therapy in multiple myeloma

Introduction: Multiple myeloma is one of the most frequent hematological malignancies. The prognosis of patients has substantially improved due to new treatment options. However, the early diagnosis is still a crucial factor for prognosis. First symptoms of myeloma are different and mostly unspecific therefore many patients are diagnosed late with serious organ and/or tissue damage. Czech Myeloma Group initiated the program for early diagnosis of MM in 2007. Program (named due to educational reasons“CRAB“) was focused on general practitioners (GPs) and key specialists responsible for recognizing the symptoms related to MM (neurology, orthopedics, nephrology). We present results of the final analysis. Methods: a/ telephonic survey for healthcare professionals, b/ written information for primary care providers, c/ brochures containing definition of clinical symptoms and recommended diagnostic methods, d/ patient questionnaire, e/ presentations at medical meetings in Czech republic, f/ presentation in non-hematological medical journals, g/ e-learning. Primary objectives were: 1) decrease risk of late diagnosis ( > 3 month after first symptoms of myeloma) from 50% to 30%, 2) reduction of irreversible deterioration at the time of diagnosis from 20% to <10%. Secondary objectives were: 3) improve knowledge of the first-contact care providers about the initial symptoms of multiple myeloma 4) inform them about diagnostic methods applicable in first-contact care 5) inform them about new treatment modalities and improving prognosis of myeloma patiens. Planned project duration was 7 years (2007-2013). The first interim analysis was done in 2010. Results: 76,4% patients was diagnosed < 3 month after first contact with healthcare professionals according to the second analysis in 2013. Probability of early diagnosed patients increased from 53,5% in 2007 to 68,8% in 2013 However, incidence of the osteolytic lesions and renal failure at time of diagnosis remained similar. Conclusion: The 7-year project leads to the increase of early diagnosis of MM by almost one third. Long-term analysis will show whether better knowledge of medical society about myeloma is transient (just during information campaign) or permanent. Project was supported by Czech Myeloma Group and JansenCillag. PO-021 A novel approach to study evolution of drug resistance and optimum therapy in multiple myeloma A. Silva, M.B. Meads, A. Distler, M. Silva, C. Cubitt, L. Perez, T.W. Jacobson, R. Baz, R.A. Gatenby, K.H. Shain Moffitt Cancer Center Departments of Malignant Hematology, Tumor Biology and Integrated Mathematical Oncology

Determinants of hypertension in a young adult Ugandan population in epidemiological transition-the MEPI-CVD survey.

BackgroundHigh blood pressure is the principal risk factor for stroke, heart failure and kidney failure in the young population in Africa. Control of hypertension is associated with a larger reduction in morbidity and mortality in younger populations compared with the elderly; however, blood pressure control efforts in the young are hampered by scarcity of data on prevalence and factors influencing awareness, treatment and control of hypertension. We aimed to describe the prevalence of prehypertension and hypertension among young adults in a peri-urban district of Uganda and the factors associated with occurrence of hypertension in this population.MethodsThis cross-sectional study was conducted between August, 2012 and May 2013 in Wakiso district, a suburban district that that encircles Kampala, Uganda’s capital city. We collected data on socio-demographic characteristics and hypertension status using a modified STEPs questionnaire from 3685 subjects aged 18–40 years selected by multistage cluster sampling. Blood pressure and anthropometric measurements were performed using standardized protocols. Fasting blood sugar and HIV status were determined using a venous blood sample. Association between hypertension status and various biosocial factors was assessed using logistic regression.ResultsThe overall prevalence of hypertension was 15 % (95 % CI 14.2 – 19.6) and 40 % were pre-hypertensive. Among the 553 hypertensive participants, 76 (13.7 %) were aware of their diagnosis and all these participants had initiated therapy with target blood pressure control attained in 20 % of treated subjects. Hypertension was significantly associated with the older age-group, male sex and obesity. There was a significantly lower prevalence of hypertension among participants with HIV OR 0.6 (95 % CI 0.4–0.8, P = 0.007).ConclusionThere is a high prevalence of high blood pressure in this young periurban population of Uganda with sub-optimal diagnosis and control. There is previously undocumented high rate of treatment, a unique finding that may be exploited to drive efforts to control hypertension. Specific programs for early diagnosis and treatment of hypertension among the young should be developed to improve control of hypertension. The relationship between HIV infection and blood pressure requires further clarification by longitudinal studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2146-y) contains supplementary material, which is available to authorized users.

Teens and Preventive Care Use: Implications for EPSDT Outreach

Teens have low overall preventive care utilization compared to other age groups. Low health care use by teens is a result of a variety of complex economic, social, and cultural factors. This study, completed by one local community health board responsible for the administration of the Early Periodic Screening Diagnosis and Treatment (EPSDT) program, produced findings that enhanced outreach to teens and supported the medical providers who serve them. More than 800 teens and young adults from a variety of cultures and communities across an urban Minnesota county were surveyed to understand the conditions under which they do and do not seek medical care. Findings suggest teens with structural barriers associated with poverty such as lack of insurance and transportation to clinics could benefit from intentional connections to medical programs. Psychosocial barriers, revolving around trust, relationships with providers, communication, and privacy, might be ameliorated through enhanced education and targeted outreach to clinics and teens, activities appropriate under the objectives and program activities of EPSDT. This study could be replicated in any community to gather data unique to local populations being served.

Cohort profile: cholangiocarcinoma screening and care program (CASCAP)

BackgroundCholangiocarcinoma (CCA) is an extremely aggressive cancer that is usually fatal. Although globally morbidity and mortality are increasing, knowledge of the disease remains limited. The Mekong region of Southeast Asia, and particularly the northeast of Thailand, has by far the highest incidence of CCA worldwide with 135.4 per 100,000 among males and 43.0 per 100,000 among females being reported in Khon Kaen Province. Most patients are first seen during late stage disease with 5-year survival being less than 10 %. Starting in 1984, control and prevention strategies have been focused on health education. Although early detection can substantially increase 5-year survival, there are currently no strategies to increase early diagnosis.Methods/designThe Cholangiocarcinoma Screening and Care Program (CASCAP) is a prospective cohort study comprising two cohorts- the screening and the patient cohorts. For the screening cohort, ultrasound examination will be carried out regularly at least annually to determine whether there is current bile duct and/or liver pathology so that the optimal screening program for early diagnosis can be established. This cohort is expected to include at least 150,000 individuals coming from high-risk areas for CCA. For the patient cohort, it is estimated that about 25,000 CCA patients will be included during the 5-year recruitment period. All CCA patients will be treated according to routine clinical care and followed so that effective surgical treatment can be formulated. This cohort is indeed a conventional cancer registry. Thus, CASCAP is an ongoing project in which the number of participants changes dynamically.DiscussionsThis is the first project on CCA that involves screening the at risk population at the community level. At the time of preparing this report, a total of 85,927 individuals have been enrolled in the screening cohort, 55.0 % of whom have already undergone ultrasound screening, and 2661 CCA cases have been enrolled in the patient cohort. Among the participants of the screening, whose mean age was 53.8 ± 9.8 years, 55.6 % were female, 77.5 % attained primary school as the highest level of education, 79.9 % were farmers, 29.9 %, reported having relatives with CCA, 89.1 % had eaten uncooked fish, and 42.2 % of those who had been tested for liver fluke were found to be infected.

Stage at presentation of breast cancer in Luanda, Angola - a retrospective study.

BackgroundIt is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country.MethodsData on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed.ResultsThe median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25–89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV).DiscussionIn this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services.ConclusionAngola needs urgently a program for early diagnosis of breast cancer.

Consolidating HIV testing in a public health laboratory for efficient and sustainable early infant diagnosis (EID) in Uganda.

Uganda introduced an HIV Early Infant Diagnosis (EID) program in 2006, and then worked to improve the laboratory, transportation, and clinical elements. Reported here are the activities involved in setting up a prospective analysis in which the Ministry of Health, with its NGO partners, determined it would be more effective and efficient to consolidate the initial eight-laboratory system for EID testing of HIV dried blood samples offered by two nongovernmental partners operating research facilities into a single well-equipped and staffed laboratory within the Ministry. A retrospective analysis confirmed that redesign reduced overhead cost per PCR test of HIV dried blood samples from US$22.20 to an average of $5. Along with the revamped system of sample collection, transportation, and result communication, Uganda has been able to vastly increase the HIV diagnosis of babies and engagement of them and their mothers in clinical care, including antiretroviral therapy. Uganda reduced turnaround times for results reporting to clinicians from more than a month in 2006 to just 2 weeks by 2014, even as samples tested increased dramatically. The next challenge is overcoming loss of babies and mothers to follow up.

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer