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Testicular cancer: the role of the primary care physician in prevention and early detection.

Early detection and screening techniques along with the concept of personal responsibility for one's own health are prominent themes in medical education. Testicular cancer, its natural history, and the current approach to prevention, early detection, and diagnosis are discussed with special emphasis on the role of the primary care physician. Current community and school efforts are described along with the availability of patient education resources. Since the incidence of testicular cancer has doubled in the last 20 years, we must give more attention to educating the public by encouraging primary physicians to incorporate instruction on self-examination of the testicles into regular physical exams.

Adolescent

Radiographic screening in the early detection of lung cancer.

A prospective study designed to detect early lung cancer in a high risk outpatient volunteer population is in progress. At present all 10,362 volunteers have been recruited into the project. A review of the radiographs of patients with lung cancer identified on the initial screen, or in retrospect, has led to the following conclusions: (1) Independent double reading is important in a screening project. (2) There are no reliable radiographic criteria to distinguish early lung cancer from benign disease. (3) The lateral chest radiograph is useful in the high risk patient. From these conclusions the authors have three recommendations for the practicing radiologist. (1) Since double reading improves sensitivity, attempt to doubly read a chest radiograph by removing your eyes from the film and look at it a second time before finalizing your report. (2) Consider any newly appearing, noncalcified lesion in the chest radiograph of a high risk individual as primary lung cancer until proven otherwise. (3) Consider the "routine chest radiograph" in a high risk patient as a challenge to detect early lung cancer rather than the drudgery of day to day clinical practice.

Aged

[Significance of early detection and early treatment of the development of children with phenylketonuria].

The amino acid l-phenylalanine (PA) accounts for 3-6 percent of all food proteins. Its breakdown is mainly through change into tyrosine. This irreversible metabolic step which makes PA an essential amino acid occurs in the liver and is catalyzed by PA-hydroxylase. In the autosome-recessive phenylketonuria syndrome (PKU, medium incidence rate 1:10,000) there is no PA-hydroxylase activity in the hepatic tissue. Infants suffering from PKU are born without any visible damage, but the untreated disease leads to irreversible brain injury. In the GDR legislation for early screening has been in force since 1971, so that the disease is recognized in all new-born babies. Brain damage can be prevented by dietetic treatment which starts during the first month but not later than the second month of life. The results of examinations performed on 107 infants suffering from PKU, with different onsets of dietetic treatment, underline the fundamental importance of early recognition and treatment for optimal development.

Child

[Early detection and early intervention--district physician's role].

In patients with established alcohol dependence or advanced alcohol abuse, medical treatment yields fairly poor results; and although early intervention may be effective in impeding the progression of incipient abuse, the problem must be brought to light in good time and the approach to intervention must be effective and easy to apply in the primary care context. The district medical officer is ideally placed to identify and deal with early alcohol problems in patients.

Alcoholism

[Coats' disease: early detection and early treatment (author's transl)].

With regard to visual prognosis Coats disease can grossly be divided in 3 different stages: If the disease is confined to the periphery of the fundus, complete recovery can be achieved by appropriate treatment. If there is already a severe macular involvement central visual acuity hardly improves, but blindness can be prevented. In case of a widespread, exsudative retinal detachment, the prognosis is unfavourable. Early diagnosis and early treatment of Coats' disease are therefore very important.

Adolescent

Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.

BACKGROUND: Early detection of HPV-associated oropharyngeal squamous cell carcinoma, the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. HPV circulating tumor DNA (ctDNA) is a sensitive and specific biomarker for HPV-associated oropharyngeal squamous cell carcinoma at diagnosis. It is unknown if ctDNA HPV is detectable prior to diagnosis, and thus its potential as an early detection test is also unknown. METHODS: Plasma samples from the Mass General Brigham Biobank collected 1.3-10.8 years prior to diagnosis from HPV-associated oropharyngeal squamous cell carcinoma patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multifeature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay. RESULTS: HPV ctDNA results were positive in 22 of 28 prediagnostic samples from HPV-associated oropharyngeal squamous cell carcinoma cases (sensitivity 79%) with a maximum lead time of 7.8 years. HPV ctDNA results were negative in all controls (0 of 28, 100% specificity). Diagnostic accuracy was highest within 4 years of cancer diagnosis and was higher than HPV Ab detection within the same timeframe (P = .004). Application of a machine-learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27 of 28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years. CONCLUSIONS: HPV ctDNA can be detected in the blood years prior to diagnosis with HPV-associated oropharyngeal squamous cell carcinoma, with high specificity, in a case-control cohort of 56 participants. HPV ctDNA detection alone, or in combination with previously identified serological biomarkers, may be a feasible approach to early detection of HPV-associated oropharyngeal squamous cell carcinoma.

Humans

Early detection of ovarian cancer: background, rationale, and structure of the Yale Early Detection Program.

Ovarian cancer has received national attention as a highly virulent disease. Its lack of early warning symptoms and the failure to develop highly sensitive screening tests have led some physicians to recommend prophylactic oophorectomies to women with relatives who have had ovarian cancer. Others have recommended routine screening of otherwise normal women for CA 125, a circulating tumor marker, and ultrasound examinations. Each of these techniques is associated with substantial false-positive rates that could lead to unnecessary surgery. A review of epidemiologic data suggests that familial ovarian cancer kindreds are rare, but women with first-degree relatives who have had ovarian cancer have a significant risk themselves for developing ovarian cancer. In addition, women with a great number of ovulatory cycles are at an increased risk for the disease. Circulating tumor markers are frequently elevated in women with advanced ovarian cancer, but their value in early detection of ovarian cancer has yet to be established. Advances in endovaginal ultrasound and color Doppler flow technology have significantly improved our ability to assess pelvic organs. This article presents the background, rationale, and structure of the Yale Early Detection Program for ovarian cancer, whose goals are to identify the best techniques for diagnosing ovarian cancer in an early stage, to determine the frequency with which such tests should be employed, to assess false-positive results, and to identify women who might benefit from prophylactic oophorectomies.

Biomarkers, Tumor

The use of electro-acoustic impedance measurements in detecting early clinical otosclerosis.

The first evidence that sodium fluoride (NaFl) can stop the otosclerotic process was recently presented. This development has placed new emphasis on the early detection of clinical otosclerosis. Electro-acoustic impedance measurements often detect minute changes in absolute impedance and compliance of the ossicular chain. The most valuable diagnostic information, however, is a negative on-off (biphasic) type of acoustic reflex. These results are often evident prior to the detection of positive clinical signs of otosclerosis. The negative on-off acoustic reflex is reviewed in this paper along with case discussions involving medical/surgical management of early otosclerosis.

Acoustic Impedance Tests

Early detection of human chorionic gonadotropin in urine by simple immunoassays.

Data are presented to show that human chorionic gonadotropin (hCG) in urine can be detected early in pregnancy by simple immunoassays performed prior to or around the time of the expected but missed menstrual period. Differences between the use of simple immunoassays with urine and radioimmunoassays and radioreceptor assays with serum are discussed.

Chorionic Gonadotropin

Computed tomography scan in the early detection of silicosis.

We evaluated the ability of both the conventional and high resolution computed tomography (CCT and HRCT, respectively) scans of the thorax to detect early silicosis in subjects exposed to silica dust in the mines and foundries of Québec for an average of 29 +/- 2 yr. The study was limited to subjects with chest radiograph (CR) of the International Labor Organization (ILO) Categories 0 or 1 as determined independently a priori. All subjects had a standard high-kilovoltage posteroanterior and lateral CR, a set of 10 to 15 1 cm collimation CCT scans, and a set of three to five 2 mm collimation HRCT scans in the upper, middle, and lower lung fields. For each CR and sets of CT scans, readings were done independently by four experienced readers. For small opacities of the lung parenchyma on CR, 32 of the 51 subjects were normal (Group A), six were indeterminate (Group B), and 13 were abnormal (Group C). By the combined readings of HRCT and CCT, 13 of the subjects (40%) in Group A were abnormal (p less than 0.001); four of the subjects in Group B were abnormal, and in Group C, one subject was normal, one indeterminate, and 11 (84%) abnormal. For confluence of small opacities, 48 of the 51 subjects were negative (Group 0), and three were positive (Group 1) on the CR. By the CT scan, 42 of the 48 subjects in Group 0 were negative, and the three subjects in Group 1 were positive; thus the CT scan added six positive cases with confluence of small opacities (six of 48, 12.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[An early detection of the recurrence of serous cystadenocarcinoma of the ovary with the tumor marker CA125 levels].

We studied whether or not, and to what extent, it was possible to predict the recurrence of serous cystadenocarcinoma of the ovary by means of the tumor marker CA125 levels, in 35 treated cases of ovarian serous cystadenocarcinoma. The relationship between the change in CA125 levels and the frequency of recurrence was examined in two groups (recurrent group and non-recurrent group). When CA125 levels over 35U/ml were defined as positive for recurrence, the true positive rate was 22/23 in the recurrent group, and 0 in the non-recurrent group. When this cut-off level was lowered to 30U/ml, and then 25U/ml, the false positive rate in the non-recurrent group was increased to 1/12 and 4/12, respectively. A three-serial increase in CA125 levels was observed at the onset of recurrent cases including two cases with CA125 levels under 35U/ml, while it was not detected in any in the non-recurrent group. Analysis of the CA125 level increase pattern with a non-linear model showed that recurrence could be detected before the CA125 level reached 100U/ml in 13/19 (68.4%) cases if the interval between CA125 measurements was one mouth, and in 17/19 (89.5%) cases if the interval was two weeks. These results suggest that possibility that recurrence can be detected early.

Adolescent

Verification of the cause of death in the trial of early detection of breast cancer. UK Trial of Early Detection of Breast Cancer Group. Trial Co-ordinating Centre.

The limitations of case review as a means of identifying errors in death certificates among breast cancer patients in a non-randomised trial of screening are illustrated by the findings of this large study. Records of 928 out of 990 deaths were available for review but were very variable in quality. Definite errors were found in 1%, errors were suspected in a further 5% and uncertainty about the cause of death, despite review, was recorded for 27%. The overall bias in reporting breast cancer deaths was less than 1%. It was concluded that the certified underlying cause of death without review provides an adequate endpoint for evaluating breast cancer screening programmes in the UK.

Age Factors

Early Childhood Development Programme--early detection.

The Early Childhood Development Programme has four main objectives. These are: 1. To foster child development in families with young children largely through personal involvement of the family in an education context. 2. To provide enrichment programmes to enrich the social, emotional and physical environment and to ensure that children with special needs have these needs met optimally. 3. To provide for the early detection of children who are more vulnerable because of the presence of a condition which may tend to limit optimal development and make the child more open to adverse influence of social or cultural pressures; that is a health assessment programme. 4. To provide a family support service for families of children with special needs to enable these families to foster and to fulfil themselves in the society in which they live. This family support service is seen as providing a structure for home centred parent/infant habilitation aimed at keeping the family in the main stream insofar as education and health are concerned.

Australia

Early detection of ovarian cancer: preliminary results of the Yale Early Detection Program.

Eighty-four women at high risk for ovarian cancer by having first-degree relatives with epithelial ovarian cancer participated in a newly established, early ovarian cancer detection program at Yale University. Participants were to be evaluated with physical examinations and circulating tumor markers at entry and every six months thereafter. Endovaginal ultrasound and color Doppler flow studies were to be performed at three and nine months following entry into the program. In addition, women were encouraged to follow American Cancer Society guidelines for mammography. Stool was checked for occult blood. Endometrial sampling was offered to post-menopausal women. No participant has developed an ovarian cancer since entering the program. One woman has been diagnosed to have breast cancer. False-positive levels of circulating tumor markers (CA 125, 4/84 [4.8 percent]; lipid-associated sialic acid in plasma, 13/84 [15.5 percent]; NB/70K, 4/84 [4.8 percent]; and urinary gonadotropin fragment, 1/65 [1.5 percent]) were observed on entry into the program. Low resistive indices (less than 0.5) were documented in 8/91 (8.8 percent) ovaries studied by the color Doppler flow technique. One participant underwent a laparotomy based on a false-positive endovaginal ultrasound examination. Tests now being employed in community practice have a high likelihood of being associated with false-positive results. Therapeutic interventions based on isolated abnormal tumor markers or ultrasound studies obtained from women with family histories of ovarian cancer may lead to inappropriate surgery. It is necessary for cancer centers to develop expertise in ovarian cancer detection techniques to advise physicians in their geographic areas appropriately about the significance of the abnormal screening test.

Adult

How advances in machine learning drive early detection and risk prediction of early-onset colorectal cancer.

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before age 50, is rising across high- and middle-income settings whilst organised screening stays anchored to older age thresholds. Blood-based liquid biopsy, combined with machine learning, is the most plausible route to early detection in this group because it does not depend on bowel preparation, endoscopy capacity, or adherence to stool-based testing. The gap is structural: incidence climbs fastest in the population below the age at which any guideline-endorsed modality is offered. The analytical challenge is that early-stage tumour-derived signals in plasma are low in abundance and distributed across heterogeneous molecular layers: circulating tumour DNA mutations, aberrant methylation, cfDNA fragmentomics, and small non-coding RNA. Machine learning converts these into a single calibrated probability. This review examines where artificial intelligence (AI)-driven liquid biopsy genuinely adds diagnostic value in EOCRC, distinguishes components in which learned models are decorative from those in which they are mechanistically necessary, and identifies the validation deficit separating research cohorts from deployable clinical tools. It summarises the first-generation tools used clinically for early detection and post-treatment monitoring, then considers analytes from exosome-bound microRNAs to long-read whole-genome sequencing of circulating plasma DNA, which reads cytosine modification natively, resolves methylation and fragmentation on single molecules, and characterises structural events short reads cannot anchor. Any analyte can feed a learned model, but more diverse input yields better discrimination. The central argument is that approved, guideline-included blood tests were validated in populations aged 45 and above, and their performance in younger patients cannot be assumed.

cfDNA fragmentomics

Liquid biopsy for early detection of pancreatic ductal adenocarcinoma.

There is no clinically relevant blood-based assay for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC), a solid malignancy characterized by poor outcomes. Here we developed, validated and tested a blood-based microRNA (miRNA) assay (which included hsa-miR-142-3p, hsa-miR-30c-5p, hsa-miR-335-5p, hsa-miR-340-5p, hsa-miR-200b-3p, hsa-miR-1260b, hsa-miR-145-3p, hsa-miR-145-5p, hsa-miR-429 and hsa-miR-200a-3p) and a composite score, PANXEON (PANcreatic cancer eXosome Early detectiON), that integrates the miRNA signature with carbohydrate antigen 19-9 for the detection of early-stage PDAC. We conducted an international, multicenter, observational, prospective biomarker study that involved 1,785 individuals with and without PDAC from four countries. The miRNA signature achieved an area under the receiver operating characteristic curve of 88.6% in the testing cohort, with a sensitivity of 83.8% for early-stage PDAC, while showing minimal cross-reactivity with other gastrointestinal cancers. In a cohort of 19 individuals, the miRNA signature levels decreased during neoadjuvant chemotherapy and after surgery and increased before disease recurrence. When combined with carbohydrate antigen 19-9 levels, this blood assay demonstrated a sensitivity of 86.8% for stage I-II PDAC, false-positive rates of 3.2% in low-risk controls and 15.6% in high-risk controls in the testing cohort. PANXEON demonstrates potential for detecting high-grade dysplasia in individuals with high-risk pancreatic cysts (64.3%). Collectively, we present a composite biomarker that may complement existing strategies for the detection of early-stage PDAC and warrants further large-scale prospective studies. ClinicalTrials.gov registration: NCT06388967 .

Journal Article