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Fatal liver failure in 16 children with valproate therapy.

The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged less than 3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, approximately 100 fatalities have been reported in relation to VPA treatment. More than 90% were aged less than 20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.

Adolescent↗

Failure of cefotaxime treatment in two children with meningitis caused by highly penicillin-resistant Streptococcus pneumoniae.

Two infants, aged 8.5 and 11 months, were admitted for meningitis caused by Streptococcus pneumoniae. Failure of cefotaxime led to the identification of highly penicillin-G-resistant strains. Minimum inhibitory concentrations (MICs) for penicillin were > 2 micrograms/ml, and cefotaxime MICs were 2 micrograms/ml. Both patients rapidly responded to a combination of i.v. imipenem and rifampicin. It is now mandatory to test in-vitro susceptibilities of Streptococcus pneumoniae to penicillin G and other beta-lactam agents when meningitis is diagnosed in infants.

Anti-Bacterial Agents↗

Comparison between the LCx Probe system and the COBAS AMPLICOR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients attending a clinic for treatment of sexually transmitted diseases in Amsterdam, The Netherlands.

Two assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae were compared: the LCx Probe system (the LCx system; Abbott Diagnostic Laboratories, North Chicago, Ill.) and the COBAS AMPLICOR C. trachomatis/N. gonorrhoeae system (the COBAS AMPLICOR system; Roche Diagnostic Systems, Branchburg, N.J.). Endocervical swab specimens, male urethral swab specimens, and female and male urine specimens were collected from 503 female and 498 male visitors attending a sexually transmitted diseases clinic in Amsterdam, The Netherlands. Prevalences for C. trachomatis were 12.5% (63 of 503) and 10.0% (50 of 498) in females and males, respectively. The prevalences for N. gonorrhoeae were 1.2% (6 of 503) and 4.2% (21 of 498) in females and males, respectively. Both assays showed high values for sensitivity and specificity with regard to the detection of C. trachomatis in endocervical swab specimens, male urethral swab specimens, and female and male urine specimens. The sensitivities for the LCx system were 92.1, 90.0, 88.9, and 94.0% for each type of specimen, respectively; and the sensitivies for the COBAS AMPLICOR system were 96.8, 98.0, 82.5, and 92.0% for each type of specimen, respectively. Specificities ranged between 98.4 and 100%. The sensitivity of the LCx system for the detection of N. gonorrhoeae was 100% for female cervical swab and urine specimens and male urethral swab specimens, while for male urine specimens the sensitivity was 95.2%; the specificity was 100% for all types of specimens. For the detection of N. gonorrhoeae by the COBAS AMPLICOR assay, the sensitivity for female cervical swab and male urethral swab specimens was 100%, that for female urine specimens was 66.7%, and that for male urine specimens was 95.2%. However, the predictive values of a positive test for female cervical swab specimens and urine specimens were 31.6 and 36.4%, respectively. Sequence analysis of the amplimers obtained by an in-house 16S rRNA PCR of the solely COBAS AMPLICOR system-positive swab specimens revealed neither N. gonorrhoeae nor other Neisseria spp. The COBAS AMPLICOR assay was considered not suitable for screening for infections with N. gonorrhoeae. If this assay is used for detection of N. gonorrhoeae, confirmation of positive results by a reliable test is mandatory.

Ambulatory Care↗

The great hijack.

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AIDS Serodiagnosis↗

Why and how to treat chronic hepatitis C.

Chronic hepatitis C (CHC) is a major health problem worldwide, with approximately 200 million affected individuals and a significant rate of progression to end-stage cirrhosis and hepatocellular carcinoma (HCC). If hepatitis C virus (HCV) infection is left untreated in the population, then the number of liver-related deaths will soon double and the need for liver transplantation may increase to five times that seen today. Available therapies for CHC are restricted to interferon alpha (IFN alpha) monotherapy and to the combination of IFN alpha and ribavirin. Despite their high cost and side effects, both of these therapies have proved to be cost effective, particularly combination therapy. IFN alpha monotherapy for one year can induce sustained response (SR) rates of approximately 10% in naive patients infected with HCV genotype 1, and above 50% in those infected with other genotypes. Combination therapy can double or even triple the rate of SR in genotype 1 infections and may further increase the SR rate in the other HCV genotypes. Combination therapy has also been proven to be effective in approximately 50% of relapsed responders to IFN alpha monotherapy. In clinical practice, the decision to treat should be individualized and tailored on the basis of several virus- and host-related factors, particularly the grade and stage of liver disease, HCV genotype and levels of viremia. Appropriate monitoring of therapy by careful clinical evaluation, liver biochemistry and serum HCV RNA testing is mandatory. IFN alpha therapy may also prove to be effective in reducing the rate of HCC development in CHC regardless of whether a virological response is achieved, but this remains to be established.

Antiviral Agents↗

Wrist measurement of blood pressure: some critical remarks to oscillometry.

UNLABELLED: Oscillometric blood pressure measuring devices worn at the wrist are preferred by a growing part of hypertensive patients for self-measurement because of their compactness and ease of use. However, little is known about the accuracy of such instruments. The accuracy of such devices was evaluated by measuring the blood pressure at the end of a coronary angiography procedure in 27 subjects nearly simultaneously in the aortic arch, using a Statham P23 transducer, and at the wrist, using the blood pressure watch (BPW) by NAIS-Matsushita. Four replicate comparative measurements were performed in each subject. On average, the blood pressure measured by the BPW was found to be higher: systolic +1.2+/-(SD)10.2 mm Hg, diastolic +4.1+/-7.2 mm Hg. The correlation coefficient between the two methods was 0.85 for the systolic and 0.84 for the diastolic pressure, but 39% of the systolic and 22% of the diastolic differences were outside the range of +/-1 SD. There was no correlation between systolic differences and blood pressure or patients' variables, but multiple regression analysis revealed that the diastolic blood pressure differences were negatively correlated with the aortic diastolic pressure (r = 0.89, p<0.001), indicating that the BPW is less accurate to detect lower values. CONCLUSIONS: (1) Though the average systolic and diastolic deviations between both methods and the relative correlation coefficients suggest that the BPW is to be used carefully for monitoring blood pressure, the great variability of differences and the inability of the BPW to detect lower diastolic blood pressure calls for a mandatory validation test by an approved protocol before this new device can be recommended for general use. (2) On the basis of our results for wrist oscillometry with the BPW and data reported in the literature for upper-arm oscillometric devices, we recommend to use oscillometric devices only when they were validated properly. In particular, the oscillometric measurement should be employed with caution for epidemiological studies or for investigation of population groups (e.g., children or pregnant women) that are expected to display lower diastolic pressures.

Adult↗

Cervical artery dissection: a 5-year prospective study in the Belluno district.

BACKGROUND: Artery dissection is an unusual cause of ischemic stroke, particularly frequent among young patients. The aim of this study was to collect epidemiological data on artery dissection in a hospital-based community, set up a diagnostic protocol and discover outcome predictors. METHODS: Among patients suffering from cerebral infarction resident in our country, those with clinical and radiological features suggestive of artery dissection were selected. Risk factors, investigative techniques and treatment were evaluated. Patients were subjected to clinical examinations and were regularly tested neuradiologically. RESULTS: Out of 895 ischemic stroke patients, 10 patients with cervical artery dissection (1.1%) were found. Seven patients were treated with anticoagulants and 3 received antiplatelet agents. One posttraumatic artery dissection patient died within a few days of the stroke. None of the patients suffered from a recurrence, while serious disability occurred in 4 of them. CONCLUSIONS: Artery dissection should be suspected in any cerebral infarction patient, especially in young patients without risk factors for cerebrovascular diseases. The treatment of choice consists of anticoagulants. An early clinical diagnosis, strongly supported by radiological tests, is mandatory to start the proper treatment and achieve the best possible outcome.

Adult↗

Sudden death during exercise.

Although death during exercise is rare, vigorous physical activity is associated with increased risk for fatality, particularly in individuals with overt cardiac disease or a high coronary risk profile. The mechanism of death is usually a lethal ventricular arrhythmia, but this may vary depending on the underlying cardiac condition. Cardiac disease is present in the great majority of individuals who die during exercise. In young persons, hypertrophic cardiomyopathy and congenital coronary anomalies are most frequent, whereas older victims usually have coronary artery atherosclerosis. Cardiac disease is typically unrecognized before the fatal event in young individuals; in the older group, most have overt coronary disease or identifiable risk factors. Screening asymptomatic subjects to identify increased cardiac risk during exercise is problematical in terms of logistics, expense and accuracy. However, careful evaluation, including exercise testing, is mandatory before a program of increased physical activity is initiated in cardiac patients. For other individuals, firm guidelines are lacking, and the extent of the evaluation must be determined on an individual basis.

Death, Sudden↗

Toxoplasma lymphadenitis. Analysis of cytologic and histopathologic criteria and correlation with serologic tests.

OBJECTIVE: To identify cases of Toxoplasma lymphadenitis by light microscopic examination of fine needle aspiration cytology (FNAC) smears and paraffin sections and to correlate the result with those of serologic tests. STUDY DESIGN: The study group consisted of 19 cases of Toxoplasma lymphadenitis, 7 of which were diagnosed by FNAC, 9 on excision biopsy and 3 on FNAC followed by biopsy. Nineteen cases of reactive lymphadenitis, tuberculosis and infectious mononucleosus composed the control group. Sera from all 38 patients were screened for antibodies to Toxoplasma. RESULTS: Eleven of 19 cases (58%) of Toxoplasma adenitis had very high titers of antibody (> 300 ELISA units/ml), and 6 cases (31%) had antibody titers in a range suggestive of active infection (210-300 ELISA units/mL) and required demonstration of rising titers. Overall, 89% of patients with Toxoplasma lymphadenitis showed significant levels of antibody. All patients from the control group showed consistently low levels of antibody to Toxoplasma. CONCLUSION: Though serologic tests are mandatory for the diagnosis of Toxoplasma lymphadenitis, a high index of suspicion can be obtained by means of light microscopy alone.

Adolescent↗