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Evaluation of urine specimen integrity in a public health STD screening program.

Detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae infection in urine using molecular amplification assays has permitted institutions with limited medical facilities to offer testing for these sexually transmitted diseases (STDs). The Nebraska Public Health Laboratory (NPHL) investigated the validity of urine samples submitted for C trachomatis and/or N gonorrhoeae amplification after receiving a substantial number of clear specimens. Approximately 75% of all urine specimens submitted for STD testing to the NPHL were from correctional facilities. The falsification of urine specimens submitted for microbiology studies is not evaluated routinely, and this problem was previously undocumented. By using the criteria for specific gravity of 1.001 or less and a creatinine concentration of less than 5 mg/dL (442 mumol/L), approximately 8% of all specimens submitted during the study interval were determined to be inconsistent with urine. The microbiology laboratory should be aware of the possibility for specimen manipulation to identify facilities submitting falsified specimens, to initiate appropriate intervention, and to minimize false-negative reporting.

Chlamydia Infections↗

Diagnostic efficacy of endovaginal color Doppler flow imaging in an ectopic pregnancy screening program.

The authors compared the diagnostic yield of endovaginal color and pulsed Doppler ultrasound (US) in conjunction with endovaginal sonography with that of endovaginal sonography alone in patients prescreened to be at increased risk for ectopic pregnancy. Pelvic structures were evaluated for overall vascularity and for the presence of characteristic pulsed Doppler US velocity waveforms. The diagnostic sensitivity of the initial endovaginal sonographic examination increased with the addition of color and pulsed Doppler US, from 71% to 87% for ectopic pregnancy, from 24% to 59% for failed intrauterine pregnancy, and from 90% to 99% for viable intrauterine pregnancy. Specificities for endovaginal sonography with color and pulsed Doppler US ranged from 99% to 100%. Use of endovaginal color and pulsed Doppler US increased the percentage of diagnostic initial sonographic examinations from 62% to 82%. The improved diagnostic sensitivity of endovaginal color Doppler US for ectopic pregnancy may ultimately result in earlier treatment, with reduced morbidity and mortality.

Color↗

Effect of bias in hematofluorometer measurements of protoporphyrin in screening programs for lead poisoning.

Values for erythrocyte protoporphyrin (EP), measured in our laboratory after extraction with ethyl acetate-acetic acid, were compared with hematofluorometer measurements made in 21 other laboratories. We found that: (a) for samples of patients' blood, hematofluorometer results were 11 to 28% lower than the extraction-based values, depending on the concentration of EP and the mathematical model used; (b) hematofluorometers had mean errors of 0 to 3% for federal proficiency-testing samples; (c) there were no performance differences between fresh and shipped blood for the six laboratories that were analyzing both; (d) a hematofluorometer with a 20% low bias at an EP concentration of 500 micrograms per liter of whole blood (by the extraction method) will not detect about a third of the children whose EP concentration exceeds that cutoff value; and (e) at this same cutoff value for EP, the extraction tests detects about 45% of children whose blood lead exceeds 300 micrograms/L, whereas a 20% low-bias hematofluorometer detects only about 37%.

Blood Specimen Collection↗

Preliminary results on the mental development of hypothyroid infants detected by the Quebec Screening Program.

A prospective study of the mental development of hypothyroid infants detected by the Quebec Network for Genetic Medicine began in January, 1976. The mean age at initiation of thyroid hormone therapy was 27 days. Forty-five hypothyroid infants and 37 normal control subjects were assessed at age 12 months with the Griffiths mental development test; 77 and 41, respectively, were assessed at age 18 months, and 59 and 40, respectively, at 36 months. There were no statistically significant differences in the various test scores between the two populations at age 12 months, but at age 18 and 36 months the hypothyroid infants had lower scores in hearing-speech performance scales and practical reasoning (36 months) which also decreased their global quotient. The mean scores were still above 100 and only nine were below 85. Further assessment of the influence of early therapy on mental development at age 6 years is needed before definitive statements can be made about the long-term mental development in these subjects.

Child, Preschool↗

Simultaneous detection of a wide variety of commonly abused drugs in a urine screening program using thin-layer identification techniques.

A single-step extraction method and thin-layer identification techniques capable of testing a wide variety of drugs of abuse are presented. These techniques are well suited for large and/or small drug programs involved in urine testing because they provide substantial economic benefits and improve clinical functioning. The drugs are absorbed on a 6 X 6 cm piece of paper loaded with cation-exchange resin and then eluted from the paper at pH 10.1 using ammonium chloride-ammonia buffer. The simultaneous thin-layer detection of sedatives, hypnotics, narcotic analgesics, central nervous system stimulants and miscellaneous drugs is accomplished by spotting the solution of extracted residue on a 20 X 20 cm Gelman pre-coated silica gel glass microfiber sheet (ITLC Type SA). A two-stage solvent system is used in order to obtain a chromatogram with optimum separation of a wide range of drugs. This system can separate methadone and/or cocaine from propoxyphene, methaqualone, methylphenidate, pentazocine, pipradrol, Doxepin, chlorpromazine, phenazocine, naloxone, naltrexone, imipramine and trimeprazine; amphetamine from phenylpropanolamine and dimethyltryptamine; codeine from dextromethorphan; methamphetamine from dimethyltryptamine, etc. Different detection reagents are then applied in succession to different marked areas of the developed chromatogram. This elegant method of extraction and spraying has enabled us to detect morphine base at a sensitivity level of 0.15 mug/ml, amphetamine sulfate at 1.0 mug/ml, methamphetamine hydrochloride at 0.5 mug/ml, phenmetrazine hydrochloride at 0.5 mug/ml, codeine phosphate at 0.5 mug/ml, methadone hydrochloride at 1.0 mug/ml, secobarbital at 0.36 mug/ml and phenobarbital at 0.5 mug/ml in urine. The minimum volume of urine needed to achieve these sensitivities is 20 ml. The cost of analysis per urine specimen using these techniques for concomitant screening of these drugs is less than US$ 1.

1-Propanol↗

Comparison of immediate and deferred colposcopy in a cervical screening program.

OBJECTIVE: To evaluate the effect of delaying colposcopy in women with negative Papanicolaou smears and positive speculoscopy results. METHODS: This was a prospective study of asymptomatic women ages 13-60 years, regularly scheduled for pelvic examinations. All women had Papanicolaou smears and magnified visual examinations with speculoscopy. Women with negative Papanicolaou smears and positive speculoscopy results were quasirandomized to immediate or deferred colposcopy groups. RESULTS: A total of 800 women completed all phases of the study, 124 of whom had negative Papanicolaou smears and positive speculoscopy results. Among 57 women who had immediate colposcopies, 64.9% had histologic evidence of neoplasia. Sixty-seven women had their scheduled colposcopies deferred for 6 months. During this period, 21% (14) were lost to follow-up and 29% (13) of those evaluated converted from speculoscopy positive to speculoscopy negative. Among the 32 (71%) women who remained speculoscopy positive, 90% were found to have histologic evidence of neoplasia on colposcopic biopsy. CONCLUSION: In women with normal Papanicolaou smears and positive speculoscopy results, the diagnostic yield can be improved by deferring colposcopy for 6 months. Deferral should be considered only for women who are reliable for follow-up.

Adolescent↗

Evaluation of mass screening program for stomach cancer.

Particular method and program of mass survey examination of gastric cancer were introduced into Miyagi Prefecture and the results accumulated during the past 14 years are presented. During this period, 1,427 cases of gastric cancer (0.18%), as well as many cases of other diseases of the stomach and duodenum, were found by the mass survey. 450 cases were those of early cancer in which invasion of carcinoma was limited to the mucosa and submucosa. The ratio of surgically confirmed early cancer cases to all the stomach cancer cases was 36.4%. Almost in all cases of early stomach cancer there were neither complaints nor clinical symptoms; that is, they were the cases of so-called preclinical cancer of the stomach. The prognosis after surgery of early stomach cancer was remarkably favorable with a five-year survival rate over 90% and the death rate due to stomach cancer was actually decreased in the surveyed population.

Adult↗

Thin-layer detection of diazepam and/or chilordiazepoxide alone or in combination with major drugs of abuse in drug abuse urine screening programs.

Three extraction procedures for the detection of diazepam, oxazepam, chlorazepate and/or chlordiazepoxide in human urines are presented. All three procedures are based on the acid hydrolysis of benzodiazepines and/or their conjugated metabolites to give the corresponding benzophenones. Procedure I involves the direct acid hydrolysis of raw urine and is recommended when the aim is to test the abuse of benzodiazepine derivatives only. Procedure II Is a two-step extraction method in which a wide variety of drugs of abuse including cocaine (test based on the detection of benzoylecgonine) are extracted by the first step using paper loaded with cation-exchange resin and the benzodiazepines are tested in the second step by the acid hydrolysis of the spent urine left after removing the ion-exchange paper. Procedure III involves the use of inert fibrous matrix and then its acid hydrolysis. The detection procedure is based on the identification of methylaminochlorobenzophenone (MACB) and aminochlorobenzophenone (ACB). MACB is detected as a yellow-colored compound while ACB is detected by spraying with Bratton-Marshall reagent. Specificity of detection of ACB has been achieved by the selection of a thin-layer developing solvent system in which sulfonamides with primary aromatic amino groups remain at the origin.

Chlordiazepoxide↗

Lack of influence of thyroid antibodies on thyroid function in the newborn infant and on a mass screening program for congenital hypothyroidism.

Data regarding the incidence and effect of maternal thyroid antibodies on neonatal thyroid function are conflicting. In order to elucidate this aspect, antimicrosomal thyroid antibodies were measured: (1) in cord serum of a normal populations, (2) in the eluate of blood spots of infants with normal filter paper spot T4 and TSH, (3) in the eluate of blood spots from our recalled population (low T4 and normal TSH), and (4) in serum of detected hypothyroid infants. The incidence of MCA with titer greater than 1/40 in cord sera was 8% (115 of 1.383). There was no statistical difference in cord serum T4' T3' or TSH concentrations in these newborn infants compared to the MCA negative population. In 1,000 spots with normal T4 and TSH, 11 or 1.1% were positive for MCA. In 1,630 spots with low T4' 18 positive cases were discovered, or 1.1%. There was excellent correlation between maternal MCA titers and newborn infant titers either in sera or spots when paired samples were available. Finally, only one of 104 detected infants with primary hypothyroidism had detectable MCA. These results indicate a high incidence (8%) of MCA in our presumed normal newborn population, MCA does not decrease serum T4' T3' and TSH concentration or filter paper spot T4 and TSH, and thyroid autoimmunity is not a frequent cause of congenital hypothyroidism.

Autoantibodies↗

The seroprevalence of the rubeola antibody in a prenatal screening program.

OBJECTIVE: To evaluate the seroprevalence of the rubeola (measles) antibody in several obstetric populations. METHODS: In this cross-sectional study, women presenting for prenatal care underwent measurement of antibodies to the rubeola virus. The study population presented for care at either an urban medical center (group I) or a suburban medical center (group II). These groups were divided further into those receiving care in a resident-supervised clinic (A) and those in a private-practice setting (B). RESULTS: A total of 768 women were tested. Seventy-five (9.8%) women had rubeola antibody titers less than or equal to 0.13 and were classified as seronegative. The lowest percentage of seronegative women (3.2%) was found at the urban resident-supervised clinic site. The highest percentage of seronegative women (20.5%) was found in the suburban resident-supervised clinic site. Women classified as seronegative were younger, with a mean age of 25.0 years. No significant difference was observed based on gravidity, parity, or care received in an urban versus suburban private-practice setting. CONCLUSION: We suggest that an appreciable number of women presenting for prenatal care may lack antibodies to the rubeola virus. In the interest of personal and public health, populations believed to be at risk may benefit from ongoing surveillance of immune status and appropriate vaccination. Additional study is necessary to define best those groups that would benefit from surveillance and vaccination.

Adult↗

Results of the implementation of liquid-based cytology-SurePath in the Ontario screening program.

BACKGROUND: The objective of the current study was to evaluate the adequacy and detection rates of SurePath after its implementation in Ontario. METHODS: The detection and adequacy rates of the SurePath liquid-based cytology system (SP-LBC) were calculated for manually reviewed slides of the year 2002. The adequacy and detection rates from this study group were compared with a historical conventional smear (CS) group from the same laboratories during the same period of the previous year. RESULTS: The SP-LBC study group consisted of 352,680 specimens with cytodiagnoses and the CS group included 378,990 specimens. The unsatisfactory rate for SP-LBC (0.24%) was less than that of the CS group (0.58%). The detection rate of atypical squamous cells (ASC+) by the SP-LBC group (4.69%) was greater than that of the CS group (3.81%), as was the detection rate of low-grade squamous intraepithelial lesions (LSIL+; 2.13% vs. 1.50% in the CS group). There was only a trend toward increased detection of high-grade squamous intraepithelial lesions (HSIL+) in the SP-LBC group (0.34%) relative to the CS group (0.31%), because the detection rate for carcinoma by SP-LBC declined. CONCLUSIONS: The implementation of SP-LBC has been followed by better specimen adequacy and detection rates for ASC+, LSIL+, and a trend of increased detection of HSIL+ relative to CS practice. To determine sensitivity rates, a histopathologic database for cervical carcinoma and precancer needs to be established.

Carcinoma, Squamous Cell↗

A mass screening program for colorectal cancer using chemical testing for occult blood in the stool.

Following five promotional and educational programs on CBS-TV news in Chicago, 54,101 Hemoccult kits were requested by the public and distributed by seven cancer detection facilities. Only 14,074 individuals completed the test. Six hundred and seventeen or 4.38% were positive. Two hundred and fifteen test positive persons failed to respond to repeated notification. In 123 positives, diagnostic tests by the private physician were considered incomplete. In 33 positives, the private physician did no further testing at all. In 152 positives, no abnormality could be found, but work-up was variable. One hundred and eighty-seven had abnormalities other than cancer, including 40 with polyps. Twenty-seven asymptomatic and two symptomatic cancers were found. Nearly two-thirds had Dukes A or B lesions, while one-third had Dukes C tumors. Public compliance in both completing kits and following through with positive results was low. Physician evaluation of positives was often incomplete. Chemical testing for occult fecal blood, when properly combined with other tests such as proctoscopy, has the potential for lowering mortality from colorectal cancer. Continued public and professional education is needed.

Colonic Neoplasms↗

[Atypical glandular cells (AGC) on Papanicolaou smears--the great challenge of cervix screening programs].

UNLABELLED: The "grey zone" diagnostic category for glandular cells in the Bethesda System 2001 (TBS 2001) has undergone significant modification since its last version in 1991. PATIENTS: The aim of the study was to follow up patients with "atypical glandular cells of undetermined significance" (AGUS)/ "atypical glandular cells" (AGC), and adenocarcinoma cytological interpretation, based on a three-year material between 2000-2002 at the Department of Cytopathology of National Institute of Oncology, Hungary. The smears were reviewed and interpreted according to TBS 2001. Histological slides were reviewed and cytohistologic correlations were investigated. RESULTS: Out of 36193 conventional Papanicolaou smears, there were 276 AGC-NOS (AGUS, favour reactive in TBS1991) and 7 AGC-favour neoplastic (AGUS, favour neoplastic in TBS 1991) (altogether 0.78%) and 35 (0.1%) adenocarcinoma interpretations. Histology was available in 136 (AGC-NOS: 106, AGC-favour neoplastic: 7 and adenocarcinoma: 23) cases. Among the followed 106 patients with AGC-NOS, there were 24 cases with concurrent "grey zone" squamous, ASC-US, interpretation. Clinically significant lesions were found in 5/7 (71%) of cases of the AGC-favour neoplastic group, and in 27/106 (25%) of the all AGC-NOS group, the difference is statistically significant. This ratio is 16/82 (20%) in the AGC-NOS only cases, while 11/24 (46%), in the AGC-NOS with concurrent ASC-US cases, the difference is statistically significant. The high-grade lesions were mostly squamous. CONCLUSION: The results suggest that AGC-NOS with concurrent ASC-US interpretation represent a group of potential patients with statistically significant higher risk of clinically significant (among them high-grade) lesions.

Adenocarcinoma↗

Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program.

Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses. We have examined the distribution of three mutations--a 4-nucleotide insertion in exon 11, a G----C transversion at a 5' splice site in intron 12, and a 269Gly----Ser amino acid substitution in exon 7--among individuals enzymatically diagnosed as carriers of Hex A deficiency. Mutation analysis included polymerase chain reaction (PCR) amplification of the relevant regions of genomic DNA, followed by allele-specific oligonucleotide hybridization; another test for heterozygosity of the exon 11 insertion was based on the formation of heteroduplex PCR fragments of low electrophoretic mobility. The percentage distribution of the exon 11, intron 12, exon 7, and unidentified mutant alleles was 73:15:4:8 among 156 Jewish carriers of Hex A deficiency and 16:0:3:81 among 51 non-Jewish carriers. Regardless of the mutation, the ancestral origin of the Jewish carriers was primarily eastern and (somewhat less often) central Europe, whereas for the non-Jewish carriers it was western Europe. Because a twelfth of the Jewish carriers and four-fifths of the non-Jewish carriers of Hex A deficiency had mutant alleles other than the three common ones tested, enzyme-based tests cannot be replaced by DNA-based tests at the present time. However, DNA-based tests for two-carrier couples could identify those at risk for the chronic/adult GM2 gangliosidoses rather than for infantile Tay-Sachs disease.

Alleles↗

[Screening program for selection of hearing loss in newborn infants instituted by the European Community].

Early identification of hearing impairment in children poses a major problem for clinical research and development. In the last two years we determined the hearing sensitivity of 1202 newborns, small infants and children. 52.4% of the children exhibited risk factors for hearing impairment in their medical history. The majority of children was referred to our department by pediatricians (52%), who first suspected hearing impairment, 40% by parents, 3.5% by otolaryngologists, 3% by educators, and 1.5% by general practitioners. The following examinations were performed: transiently evoked otoacoustic emissions (TEOAE), impedance audiometry, auropalpebralreflex, behavioral observation audiometry, and, if necessary, auditory brain stem response (ABR) with air and bone-conducted clicks as well as frequency-following responses at 500 Hz tone burst. In 378 children TEOAE were recorded on both sides, in 151 at least on one side. These results were confirmed by the other techniques. Only three children presented false negative results of TEOAE on one side. Two of these children had a middle ear effusion and a threshold of 35 dB, one had retrocochlear hearing loss. The absence of TEOAE in both ears in 155 children as well as in one ear in 16 children was detected by ABR. Seventy-seven patients showed no response on both sides, 25 on one side, although a hearing impairment more than 25 dB could not be verified by ABR. This high number of false positive results is explained in 77 cases (76%) by a middle ear dysfunction during the recording of TEOAE, when ABR was performed following adenotomy and paracentesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The centralized prenatal genetics screening program of New York City: II. Establishment of prenatal diagnosis laboratory.

Prenatal diagnosis of genetic disorders is now being made available to an increasing number of New York City women through the establishment of a large centralized laboratory. This laboratory contracts to provide genetic diagnostic services to municipal and private hospitals throughout the New York City area. It is the first project of such magnitude in the United States. Prior to the receipt of samples for diagnostic purposes, the laboratory was required to meet the highest technical standards, as established by a Cytogenetics Advisory Committee. A set of guidelines was drawn up detailing the procedure and protocols for all the analyses and the reporting of results, including a timetable according to which results were to be obtained. The Cytogenetics Advisory Committee continues to review cases on a regular schedule. One of the unique aspects of the laboratory has been the development of back-up agreements with other area laboratories to assist in dealing with any problem that might disrupt the routine diagnostic service. The first year of operation of the laboratory has shown that financial, legal, and physical problems associated with designing and instituting a megacenter can be over-come. Similar programs should be encouraged.

Female↗