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[Early detection of congenital hypothyroidism by TSH radioimmunoassay using filter paper blood samples (author's transl)].

It has been reported that mental retardation due to congenital hypothyroidism can be prevented by early detection and early adequate replacement therapy. We have developed a radioimmunoassay for TSH using the dried blood spot and have started screening for newborn congenital hypothyroidism using a part of sample of the inborn metabolic error screening. (1) The dried blood spot TSH of 61,000 newborn infants was assayed in the first half of our screening and that of 74,505 newborn infants was assayed in the latter half of our screening. As a result, although we were not able to detect any cases in the first screening, we were able to detect 9 cases of congenital hypothyroidism in the latter screening. From the results obtained through our investigation of the thyroid function of these 9 infants, we confirmed that mild hypothyroidism can be better detected by the screening of TSH. (2) As to the program of the screening, we chose from the latter half of our screening all the samples in which TSH concentrations contained above 3 percent of each assay and were remeasured on the next assay. (3) As we confirmed that the sensitivity of measurement was increased at very low concentrations, when the volume of antibodies, radioisotopes and eluates used for each assay were decreased, we measured TSH successfully using two 3 mm discs. (4) As we can perform very simple screening by the 3 mm disc method, we are changing the screening method from that with 10 mm disc to one with two 3 mm discs. We intend to extend our screening, and will make every effort to prevent mental retardation due to congenital hypothyroidism.

Blood Preservation

Epigenetic Profiling for Early Detection and Treatment Response Monitoring in Non-Small Cell Lung Cancer: Protocol for a Prospective Translational Biomarker Study.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and continues to have poor survival outcomes, with most patients diagnosed at advanced stages of disease. In New Zealand, NSCLC contributes substantially to cancer inequities, with Māori communities experiencing disproportionately high incidence and mortality rates. Although low-dose computed tomography screening can improve early detection, major limitations remain, including false-positive findings, overdiagnosis, high infrastructure costs, and limited accessibility for rural and underserved populations. Liquid biopsy approaches using circulating tumor DNA (ctDNA), particularly DNA methylation profiling, have emerged as promising, minimally invasive strategies for improving cancer detection, treatment monitoring, and precision oncology. OBJECTIVE: This study aims to establish integrated genomic and epigenomic predictive and prognostic biomarkers using ctDNA, tumor tissue, and transcriptomic profiling to improve early detection, risk stratification, treatment selection and response prediction, and longitudinal monitoring, with particular emphasis on identifying molecular mechanisms associated with treatment resistance and disease progression. METHODS: This prospective observational translational biomarker study is being conducted through the University of Otago and associated respiratory and oncology services in New Zealand. The study will recruit participants with NSCLC (including squamous and nonsquamous subtypes), individuals referred to fast-track lung nodule assessment clinics, and nonmalignant respiratory controls. Serial peripheral blood sampling will be performed in selected participants at predefined clinical follow-up time points to evaluate treatment response and disease progression. The availability of formalin-fixed paraffin-embedded archival tissues will be recorded, but will not be mandatory for enrollment. Genome-scale DNA methylation profiling will be performed using cell-free reduced representation bisulfite sequencing (cfRRBS), while targeted genomic profiling and transcriptomic analyses will be conducted using targeted sequencing panels and RNA sequencing. Integrative bioinformatic analyses will be used to identify molecular biomarkers associated with early-stage disease, advanced disease, treatment response, and therapeutic resistance. RESULTS: Ethics approval for the study has been obtained from the New Zealand Health and Disability Ethics Committee (2022 EXP 12566). This study commenced in 2022, and recruitment and biospecimen collection are ongoing. The study aims to recruit approximately 450 participants, including patients with NSCLC, individuals referred through respiratory diagnostic pathways, and nonmalignant controls. As of July 31, 2026, 205 participants have been recruited, with recruitment continuing until the target sample size is reached. Molecular and data analyses are ongoing, with additional publications expected as the cohort matures. CONCLUSIONS: This study will generate one of the first integrated genomic, epigenomic, and transcriptomic liquid biopsy datasets for NSCLC in New Zealand. The findings are expected to support the development of sensitive, accessible, and equitable blood-based biomarkers for NSCLC detection and treatment monitoring while also contributing to improved precision oncology approaches and reducing NSCLC inequities among Māori populations.

Humans

Early detection of chronic obstructive pulmonary disease using radionuclide lung-imaging procedures.

One hundred subjects answered a respiratory questionnaire and underwent a physical examination, tests of pulmonary function, and three radionuclide lung-imaging procedures. The results of the radionuclide procedures were compared with each other and with pulmonary function tests and other diagnostic findings to determine their relative sensitivity for detecting evidence of early obstructive airway disease. Perfusion lung imaging was less sensitive than most of the other diagnostic tests evaluated. The aerosol and xenon lung-imaging procedures revealed abnormalities with approximately the same frequency as each other, but more often than any one group of pulmonary function tests, including spirometric data, maximal expiratory flow-volume curves, alveolararterial oxygen gradient, or indices derived from single-breath nitrogen washout. We concluded that xenon and aerosol lung-imaging studies are sensitive and useful screening procedures for detecting evidence of early localized obstructive airway disease and for locating regional abnormalities in the airways of patients with respiratory disease.

Adolescent

Detecting early colon cancer.

Techniques enabling detection of early colon cancer already exist, but to be more productive in terms of improving survival they must be applied in a meaningful sequence and repeated regularly in high-risk patients. Positive findings in specific screening steps based on well-known risk factors in colon cancer always call for aggressive follow-up. The advantages and disadvantages of the various techniques are discussed.

Barium Sulfate

Cell-free DNA methylation biomarkers for the early detection and tumor burden monitoring of gastric cancer.

Development of sensitive biomarkers is required to achieve early detection and tumor burden monitoring in gastric cancer (GC). We performed genome-wide methylation sequencing on 78 tissue and 241 plasma samples from 171 GC patients and 114 healthy controls from two independent clinical centers. Differentially methylated regions (DMRs) were screened using paired GC and normal tissues, and refined through cfDNA profiles with LASSO regression to construct a cfDNA-based biomarker, the GCML-score. The GCML-score, consisting of 13 DMRs, demonstrated excellent diagnostic performance (AUC: 0.95/0.99/0.95 overall and 0.96/0.99/0.82 in early GC for training/internal validation/external validation cohorts). In 12 patients receiving neoadjuvant chemotherapy, dynamic changes in GCML-score were consistent with radiological tumor burden, highlighting its monitoring potential. The GCML-score, derived from genome-wide cfDNA methylation profiling, provides a robust tool for early GC detection and real-time tumor burden monitoring, facilitating improved prognosis and personalized therapeutic strategies.

Journal Article

A multi-analyte cfDNA-based blood test for early detection of hepatocellular carcinoma.

BACKGROUND & AIMS: Patients at high risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound surveillance; however, ultrasound has low sensitivity for small HCC nodules and is associated with poor adherence. To address these limitations, the multianalyte HelioLiver Dx blood test was developed to aid in the detection of HCC in patients with cirrhosis who are at high risk for HCC. METHODS: The performance of the HelioLiver Dx test and ultrasound for the detection of HCC in adults with cirrhosis was evaluated in a cross-sectional, prospective, blinded, multicenter validation study. All participants provided blood specimens for the HelioLiver Dx test and underwent ultrasound. All participants also underwent multiphasic MRI, which served as the reference standard for determining HCC status. RESULTS: Of 1,268 evaluable participants, 46 (3.6%) were considered to have HCC as determined by MRI, with many (46%) having small HCC lesions ≤2 cm in diameter. The HelioLiver Dx test had a sensitivity of 47.8% (95% CI 32.9-63.1) for all HCC lesions and 28.6% (95% CI 11.3-52.2) for HCC lesions ≤2 cm. In contrast, ultrasound demonstrated a lower sensitivity of 28.3% (95% CI 16.0-43.5) for all HCC lesions and failed to detect any (0%; 95% CI 0.0-16.1) HCC lesions ≤2 cm. The specificity of HelioLiver Dx and ultrasound were 87.6% (95% CI 85.6-89.4) and 93.9% (95% CI 92.5-95.2), respectively. The HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound. CONCLUSION: Compared with ultrasound and alpha-fetoprotein, the HelioLiver Dx test identified more HCC lesions overall, including more small lesions. A convenient and accurate blood-based test may improve HCC surveillance by facilitating earlier detection and reducing patient barriers to testing. GOV IDENTIFIER: NCT03694600 IMPACT AND IMPLICATIONS: There is a significant, unmet clinical need for more sensitive and accessible methods for the early detection of hepatocellular carcinoma (HCC) in high-risk patient populations. The current study is the first blinded, multicenter, prospective study to evaluate the performance of a multianalyte blood test compared to abdominal ultrasound for the detection of HCC among patients with cirrhosis. The multianalyte HelioLiver Dx test met prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared to ultrasound for detection of HCC lesions. The availability of a more accessible, convenient and sensitive blood test to aid in the detection of HCC may improve utilization and consequently clinical outcomes for high-risk patients via reduction of care barriers and improved early HCC detection. CLINICALTRIALS: gov identifier: NCT03694600.

Humans

The early detection of childhood deafness.

Early commencement of habilitative measures is vital for a deaf child's development. This implies a need for early diagnosis. Some improvement has occurred in recent years, but early diagnosis is still the exception rather than the rule. To determine some of the factors which lead to early diagnosis, a survey of parents of young Australian deaf children was undertaken. This showed that, while the majority of children were suspected to be deaf on the basis of informal observation by parents, relatives or friends, the most consistent early diagnosis came as a result of follow up of infants at risk. Certain factors acted to delay diagnosis. Dissuasion and inappropriate advice from doctors significantly delayed diagnosis in 25% of all cases. Further, over half the hearing-impaired children who were tested in screening programmes were not detected, and the false sense of security given the parents in these cases resulted in long delays before suspicion of deafness (based on informal observation) developed. If early diagnosis of deafness is to become the rule, a purposeful attempt to use risk criteria, coupled with improved screening programmes, will be the most promising avenues to follow. Improved education of the community at large may also assist, but this is a much longer-term aim.

Australia

Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium.

Individuals with hereditary cancer syndromes are born with germline genetic variants that significantly increase their lifetime risk of developing multiple cancers. Cancer rates and overall mortality can be reduced with intensive surveillance to facilitate early cancer detection. However, participating in diagnostic imaging and endoscopy surveillance programs is often time-consuming, overwhelming, inconvenient, and anxiety-inducing. To improve this, multi-cancer early detection tests are being developed using cell-free DNA (cfDNA) sequencing analysis to detect cancers with more sensitivity than conventional screening methods. Our community (the CHARM consortium: Cell-free DNA in Hereditary And high-Risk Malignancies) has been exploring the use of cfDNA sequencing in hereditary cancer, and has launched the CHARM2 prospective randomized controlled trial, which is enrolling 1000 participants with Hereditary Breast and Ovarian Cancer, Lynch syndrome, Li-Fraumeni syndrome, Neurofibromatosis type 1 and Hereditary Diffuse Gastric Cancer to improve equitable access, early detection and surveillance for high-risk individuals. All participants will have screening as per conventional syndrome-specific surveillance recommendations. Half the participants (experimental cohort) will also have cfDNA analysis at least three times a year, with abnormal results triggering dedicated clinical imaging and diagnostic evaluation, and heightened surveillance. Vetted by our patient advisors, validated patient-reported outcome and experience measures assessing participant psychosocial outcomes, engagement, and test preferences will be administered to both arms. Our goal is to inform if and how cfDNA analysis could be implemented into routine clinical care and offer a path to equitable and more convenient cancer screening for all high-risk Canadians.

Female

[Organization of mass-screening for early detection of cervical cancer and its precancerous conditions. II. report: Practical experience with a computer assisted mass-screening program (Model Rostock) (author's transl)].

Two years experiences with a computerassisted program for early detection of prestages and early cervical cancer in Rostock-city are reported. From 43.000 women invited to take part in the examination, 27.028 = 65% finally cooperated. Pathological Pap-smears were found in 134 cases (= 0,52%). Histological examination in 51 cases (= 0,2%) showed 1 Erosio vera (false positive), 9 severe dysplasia, 30 carcinomata in situ, 3 early invasions (microinvasive cancer), 3 microcarcinoma and 5 macrocarcinoma. Accessory findings were seen in 10,2%. A good organized mass-screening-system with unique nomenclature, diagnostic and treatment of cervical cancer and its prestages gives the best supposition to cut down its rate of incidence.

Adult

[The value of scintigraphy for the early detection of osteomyelitis (author's transl)].

For therapy and development of acute haematogenic osteomyelitis early detection of this disease is decisive. In our study 74 children were investigated scintigraphically with Tc-pyrophosphat because of suspicion of an inflammatory bone process. In all 23 cases of osteomyelitis scintigraphy showed an indication in form of increased activity in the respective bones; so the sensivity of this investigation, found in our study, was 1.0. In 10 of 51 cases without osteomyelitis scintigraphy, however, also showed increased activity. Because of this limited specifity of scanning further investigations are needed in the diagnosis of osteomyelitis. The main advantage of scintigraphy as compared with roentgen observation is the high sensitivity in the first days of illness. In addition scanning may supply valuable informations about the inflammatory process as long as it is active.

Child

Sensitivity of radionuclide brain scan and computed tomography in early detection of viral meningoencephalitis.

The sensitivity of radionuclide imaging and computed tomography (CT) was evaluated in 25 patients for early detection of viral meningoencephalitis. Diagnosis was based on clinical evidence, cerebrospinal fluid (CSF) studies, electroencephalography (EEG) and radionuclide imaging. Computed tomography with contrast enhancement was performed within four days after onset of neurological signs or symptoms in 23 patients; no significant findings such as low-absorption abnormalities, mass effect or abnormal enhancement were seen. Radionuclide imaging demonstrated a sensitivity of 90% in the detection of viral meningoencephalitis; the temporal lobe was most commonly involved in patients with herpes encephalitis. Radionuclide imaging should be considered as the first diagnostic procedure in suspected early viral meningoencephalitis.

Adolescent

[Early detection of bronchial cancer (author's transl)].

Compared with the results of a retrospective study (1954) of early detecting bronchial cancer, our present investigations showed, that females are relatively more concerned than formerly, that the climax of frequency has removed for about ten years to the aged, that more non-smokers are concerned than formerly (16% to 3.5% respectively) and that the time between manifestation of the first symptoms and admittance to hospital has shortened remarkably (one month 26%, three months 33% = 59% compared with 28.3%). In four patients the disease has been discovered by x-ray mass-screening, two of them were nevertheless admitted to hospital too late. Whereas the value of tomography has been established, the results of bronchoscopy ameliorated. Only one patient could be operated: perhaps the shift of age for one decade and a certain negative selection may be responsible for these disappointing results. The x-ray-examination in 2 levels must be performed in every adult male patient, even if bronchopulmonal symptoms do not exist. Moreover, exposed persons (e.g. strong smokers) must be controlled by x-ray examination in regular intervals. It is in this sense, that we see the scope of x-ray mass-screening.

Age Factors

Early detection of pemphigus vulgaris.

Two cases of pemphigus vulgaris are described. These cases showed that, using the direct method of immunofluorescence, early detection of the disease was possible when repeated blood investigations had failed to show circulating antibodies to the intercellular cement by the indirect method.

Female

[Early detection of bronchial carcinoma by annual mass X ray screening (author's transl)].

Further investigations of the study group for the early detection of lung cancer in the GDR have confirmed previous conclusions that annual x-ray screening of the chest significantly improves the results of surgical treatment of cancer of the lung. The study now covers 15,336 cases operated upon between 1949 and 1976. Two thirds of all cases treated surgically in the period from 1963 to 1972 were detected by roentgenologic screening. In the screening group the 5-year survival rates after resection were more favourable than in the clinical group: 36% in 1,915 screening cases and 29% in 785 clinical cases in the period from 1965 to 1968. The percentage of peripheral lesions which were treated by lobectomy was significantly higher in the screening group. Since the introduction of a biannual mode of screening, the overall results have worsened because the number of cases detected by x-ray screening has decreased.

Carcinoma, Bronchogenic

Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing.

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.

Adolescent

Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography.

Optic disc edema (ODE) due to chronic intracranial hypertension was produced experimentally in rhesus monkeys. Serial studies of fundus changes at frequent intervals, by routine ophthalmoscopy, steroscopic color photography, and fluorescein angiography, revealed that swelling of the optic disc was the first sign of ODE. Other early signs were striation of nerve fibers on the optic disc margins and peripapillary retina, blurring of the disc margins, hyperemia of the disc and capillary dilation, hemorrhages, and other retinal vascular changes; these usually appeared in that sequence. The classically described signs of early ODE were almost always absent. A normal fluorescein fundus angiogram during the incipient stage did not rule out ODE. Stereoscopic color fundus photography was the most sensitive means of detecting early ODE. Fluorescein angiography did not show changes till edema was of a mild to moderate degree; routine ophthalmoscopy was the least reliable method.

Aneurysm