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[Autologous blood transfusion in the Federal Republic of Germany--results of a questionnaire in 1993. 2. The use of autologous transfusion in the old and new federation].

In 1993, we conducted a postal survey to assess the use of autologous blood transfusion (ABT) in the Federal Republic of Germany after reunification. The results of this survey have already been reported in a previous paper, but without differentiation between the "old" and "new" states (former West Germany and former German Democratic Republic, respectively). In the present study, the data of our 1993 survey were further analysed to see if there were differences in the use of ABT between the "old" and "new" states. METHODS. The study is based on data of a 1993 postal survey of German hospitals. Details concerning the performance of the survey have been reported in a previous paper. Briefly, questionnaires were mailed to the anaesthesia departments of 400 randomly selected hospitals in the "old" states and 284 hospitals in the "new" states of the Federal Republic of Germany. The questionnaires contained 36 questions related to general information on the hospital and the use of ABT; 305 completed questionnaires were returned from the "old" states and 197 from the "new" states, response rates of 76% and 69%, respectively. For the present investigation, the responses of the hospitals of the "old" and "new" states were analysed separately. Frequency distributions of categorical variables were analysed by the chi-square test. Because of multiple testing, statistical significance was attained only at the 0.05% level (P < or = 0.0005). RESULTS. There were no significant differences between the "old" and "new" states with respect to hospital size by number of beds, percentage of general and specialised hospitals, and percentage of operations requiring blood transfusion. In both the "old" and "new" states, 9% of the responding hospitals maintained a hospital-based transfusion service, while the other depended on regional blood banks. Preoperative autologous blood donation (PABD) was performed at least "rarely" in 85% and 71% (P = 0.0001), and "mostly" in 20% and 10% (P = 0.0014) of the hospitals in the "old" and "new" states, respectively. Uniformly, the principal uses of PABD were for orthopaedic and cardiac surgery. In 62% and 27% (P < 0.0001) of those hospitals that reported performing PABD, the autologous blood service was run by the anaesthesia department. Preoperative plasmapheresis was performed in 14% and 8% (P = 0.008), and isovolaemic haemodilution in 82% and 56% (P < 0.0001) of the hospitals in the "old" and "new" states, respectively. Automated autotransfusion devices (cell savers) were available in 38% and 19% (P < 0.0001) of the hospitals, respectively. Simple collection devices for perioperative blood salvage were used in 17% and 15% (P = 0.24) of the hospitals in the "old" and "new" states, respectively. CONCLUSION. We conclude that ABT is more widely used in the "old" than the "new" states of the Federal Republic of Germany. ABT is regarded as a desirable alternative to homologous blood transfusion, and in the interest of equal standards of medical care throughout the nation, the use of ABT should be further promoted, especially in the "new" states of the Federal Republic of Germany.

Blood Transfusion, Autologous↗

Head-trunk coordination in elderly subjects during linear anterior-posterior translations.

This study examined whether the head of elderly subjects was less stable in space when the trunk was free to move than when the trunk was fixed to a linearly moving platform. Fourteen healthy elderly subjects were seated on a linear sled with their trunk either fixed to the seat or free to move. Subjects received 10 cm, 445 cm/s2 anterior-posterior ramps and 0.35-4.05 Hz sum-of-sines translations while performing a mental distraction task in the dark. Kinematics of the head and trunk were derived from an Optotrak motion analysis system and a linear accelerometer placed on the head. Electromyographic (EMG) signals were collected for neck and paraspinal muscles. Data were tested for significance with paired t-tests corrected for multiple testing and compared (Mann-Whitney U-test) with previously published data from 12 healthy young adults (Keshner 2003). Linear acceleration trajectories of the head corresponded to the direction of sled linear acceleration when the trunk was fixed and countered the direction of the sled when the trunk was free. Angular head accelerations countered the sled or the trunk when the trunk was fixed or free, respectively. Peak amplitudes of head angular acceleration in space were greater with a fixed trunk. With the trunk free, amplitudes of head linear peak acceleration, angular accelerations, and response gains exceeded those of the young adults. Muscle EMG response latencies did not vary with the timing of head acceleration onset but the neck muscles were activated more frequently in a direction consistent with a vestibulocollic or cervicocollic reflex. Differences in angular motion of the head could be explained by the biomechanical constraints of the two tasks having one freely moving mass (head) with the trunk fixed and two freely moving masses (head and trunk) with the trunk free. These data suggest that elderly subjects rely upon active trunk mechanics in order to coordinate their head and trunk motion; however, a contribution by vestibular and ascending segmental inputs cannot be completely ruled out. A less flexible trunk in the elderly could explain why they were not as successful as young adults in stabilizing their heads in space when the trunk was free to move.

Abdomen↗

Etiology of anemia in patients with advanced heart failure.

OBJECTIVES: We prospectively investigated the causes of anemia in patients with advanced congestive heart failure (CHF). BACKGROUND: Anemia is common in patients with advanced CHF, and its etiology is generally considered to be multifactorial. However, despite its importance, precise information is lacking regarding the prevalence of putative etiologic factors. METHODS: Patients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of "clinically significant" anemia, defined as a hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a serum creatinine concentration >3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included. The initial evaluation included measurements of vitamin B(12), folic acid, thyroid-stimulating hormone, erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests, and bone marrow aspiration. Patients without diagnosis by these methods underwent red cell mass measurement with (51)Cr assay. RESULTS: The mean age of the 37 patients was 57.9 +/- 10.9 years and mean left ventricular ejection fraction 22.5 +/- 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who were considered to have "anemia of chronic disease." Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population. CONCLUSIONS: In this group of patients, iron deficiency was the most common cause of anemia. The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions.

Aged↗

Proteasome gene upregulation: a possible mechanism for intestinal adaptation.

BACKGROUND/PURPOSE: The mechanisms that control intestinal adaptation remain unknown. To better understand the adaptive process, microarray technology was used to analyze gene expression in a rat model of intestinal adaptation. METHODS: Adult male Sprague-Dawley rats underwent either a massive small bowel resection (70%) with anastomosis or a sham operation with small bowel transection and reanastomosis. After 21 days, ileal mucosa RNA was extracted. Individual RNA samples (n = 5 per group) were labeled and hybridized to 10 separate RAE 230A rat GeneChips. The signal values were calculated and the 2 groups were compared using a t test with the multiple testing correction of Benjamini and Hochberg (false discovery rate of 10%). Probe sets were analyzed for overrepresented physiologic pathways using Expression Analysis Systematic Explorer (EASE). RESULTS: Of the 15,866 probe sets on the RAE 230A GeneChip, 5437 probe sets were unexpressed and excluded. Of the remaining 10,429 probe sets, several overrepresented pathways (EASE score <0.01 after Bonferroni correction) were identified. Further analysis revealed that 13 probe sets related to proteasome degradation (an enzyme complex implicated in the regulation of cell proliferation) were significantly upregulated in the intestinal adaptation group compared to the sham group. CONCLUSIONS: Proteasomes may play a critical role in regulating the proliferation of intestinal mucosa during intestinal adaptation.

Adaptation, Physiological↗

Chemosensitivity testing of small cell lung cancer using the MTT assay.

A simple colorimetric test, the MTT assay, has been adapted for chemosensitivity testing of human small cell lung cancer cell lines, and fresh tumour samples. Optimal conditions for clinical chemosensitivity testing were determined using established SCLC lines. Nineteen different chemotherapeutic agents were tested, and sixteen of them were found to be cytotoxic in this assay system. The drug sensitivity of a panel of 16 SCLC cell lines was measured and compared. There was very little intraexperiment variation, but the interexperiment variation was significant. Cell lines which were derived from patients who had not received chemotherapy at the time the cell line was established were more sensitive (to all but one of the drugs) than lines derived from treated patients, and the differences were statistically significant for two of the drugs. One cell line, NCI-H209, which was derived from an untreated patient, stood out as being the most sensitive or among the most sensitive to all of the drugs tested. Another cell line, H69AR, which is a multidrug resistant subline of the cell line NCI-H69, was the most resistant to many of the natural product drugs tested. Multiple drug chemosensitivity testing was performed on eight fresh tumour samples from SCLC patients (five pleural effusions, one lymph node, and two primary tumours). It was possible to perform chemosensitivity testing on all of the clinical samples in which sufficient tumour cells were available. The drug sensitivity of the clinical samples was, in most cases, within the same range as for the cell lines. Since this assay is very rapid and simple to perform, it may have practical applications in clinical drug sensitivity testing of human tumours.

Antineoplastic Agents↗

T-rex: standardized analysis of germline variants in whole-exome sequencing trios.

Whole-exome sequencing (WES) enables the identification of rare germline variants contributing to pediatric diseases. Trio-based sequencing, comparing affected children with their parents, is particularly effective for rare disease genetics. However, WES data analysis requires bioinformatics expertise, varies across institutions, and is often incompatible with clinical workflows. We developed T-Rex (Trio Rare variant analysis of EXomes), a cross-platform desktop application that enables the standardized and local analysis of WES germline Trio data without the need for programming knowledge. T-Rex integrates state-of-the-art tools for alignment, dual-variant calling (GATK HaplotypeCaller&#x2009;+&#x2009;VarScan2), annotation (SNPEff/SNPSift), rare-variant filtering based on population frequencies (gnomAD), and family-based statistical testing, including the Transmission Disequilibrium Test with multiple-testing correction. Benchmarking of the dual-caller strategy on the Genome in a Bottle Ashkenazim Trio demonstrates high precision (99.2%) while maintaining robust sensitivity (91.1%). User testing (n&#x2009;=&#x2009;13) confirmed quick learning across clinicians and researchers. Application to a cohort of n&#x2009;=&#x2009;121 pediatric cancer Trio datasets, filtering for rare protein-coding variants (MAF&#x2009;&#x2264;&#x2009;0.1% in gnomAD v4.1), validated all assessable previously reported pathogenic variants. Overall, T-Rex enables clinicians to robustly analyze WES Trio data in compliance with data protection regulations without requiring additional software licenses. As one of the first platforms for comprehensive WES Trio analysis that requires no programming expertise while providing reproducible, end-to-end workflows for clinical genomics, T-Rex facilitates collaborative research between clinics and reduces reliance on external providers.

Humans↗

Accuracy in the diagnosis of short-segment Barrett's esophagus: the role of endoscopic experience.

BACKGROUND: The diagnosis of Barrett's esophagus is based on histologic demonstration of specialized intestinal metaplasia. Experience may be important in the endoscopic recognition of Barrett's esophagus, including in regard to appropriate procurement of biopsy specimens. The aim of this study was to assess factors that may influence accuracy in the diagnosis of short-segment Barrett's esophagus (SSB). METHODS: Endoscopy reports pertaining to procedures performed over a 1-year period that included esophageal biopsies because of suspected intestinal metaplasia were reviewed. Barrett's epithelium involving less than 2 cm of the distal esophagus was considered SSB; greater than 2 cm was considered long-segment (LSB). Endoscopists were regarded as "more experienced" if they had completed training more than 5 years earlier and "less experienced" if the time elapsed since the completion of training was less than 5 years. RESULTS: More and less experienced endoscopists both obtained esophageal biopsy specimens because of suspected Barrett's esophagus at the same rate (14%). Length of suspected Barrett's epithelium was not predicted by symptoms or demographic data. Endoscopically, patients with SSB had significantly fewer (64.2% vs. 90.8%) and smaller (2.9 +/- 0.1 vs. 3.5 +/- 0.2 cm) hiatal hernias compared with those with LSB (p < 0.05). Suspected SSB was histologically confirmed in 38.4% (True SSB), whereas LSB was confirmed in 75% (True SSB) (p < 0.05). More experienced endoscopists were significantly more likely to obtain histologic confirmation of SSB than less experienced endoscopists (48.6% vs. 29.5%; p = 0.02, nominal significance from univariate hypothesis testing; correction for multiple testing of data removed significance at the p < 0.05 level; OR = 2.26). CONCLUSION: With greater experience, an endoscopist is more likely to diagnose SSB. This may be due to more accurate procurement of adequate tissue samples, which thereby results in a greater yield of histopathologic diagnoses.

Barrett Esophagus↗

Sleepiness, alertness and performance during a laboratory simulation of an acute shift of the wake-sleep cycle.

Monitoring the presence of sleepiness on the job and its effects on performance is of primary importance for improving schedule systems of shiftworkers. Shiftworkers, often involved in night-time operations and irregular work schedules, frequently complain of nocturnal sleepiness especially in conditions of abrupt shift of the wake-sleep cycle. In this study, the authors evaluated the effects of a laboratory simulation of acute night-shift changes on sleepiness, vigilance and performance, using Maintenance of Wakefulness Test, Multiple Sleep Latency Test and three pencil and paper tests: Digit Symbol Substitution Test, 'Deux Barrages' Test and a 3-Letter Cancellation Task. All of the tests were administered four times at 2-hourly intervals during the night after daytime sleep. Results showed that the ability to maintain wakefulness and to perform simple visuo-attentive tasks is substantially spared during the night. On the other hand, sleep tendency and performance on a more complex and monotonous task (Letter Cancellation Task) reveal, respectively, increasing sleepiness and degrading performance.

Adult↗

The effect of marker heterozygosity on the power to detect linkage disequilibrium.

The relationship between marker heterozygosity and the power to detect linkage disequilibrium is examined through the analysis of an example and through a simulation study. The analysis suggests that, despite the penalties for multiple testing incurred with multiple alleles, greater heterozygosity results in greater power. The results of the simulation study are in accord with those of the analysis.

Genetic Markers↗

Effects of DSIP on narcolepsy.

Repeated injections of delta sleep-inducing peptide (DSIP) were given to a 35-year-old male narcoleptic. Effects on wakefulness and sleep were evaluated by self-reports, performance tests, multiple sleep latency test and all-night polysomnography. DSIP reduced the frequency of sleep attacks and increased activity, alertness and performance during day-time. The sleep period was compressed by DSIP with enhancement of REM sleep. The results suggest that the effects are due to an accentuation of circadian and ultradian rhythms by DSIP.

Adult↗

Myotonia and the muscle chloride channel: dominant mutations show variable penetrance and founder effect.

The delayed relaxation or sustained contraction of skeletal muscle-myotonia-is frequently seen in myotonic dystrophy and sodium channelopathies (hyperkalemic periodic paralysis, paramyotonia congenita). Many cases of congenital myotonia without other clinical symptoms have been associated with mutations in the muscle chloride channel gene. Most cases reported to date show a recessive inheritance pattern, with loss of function of the corresponding protein. Six families have been reported with dominantly inherited myotonia and mutations of the chloride channel gene. Here we report clinical and molecular data on 38 family members from four new families with dominantly inherited myotonia congenita. Three families show a previously characterized G230E mutation, and we show that these three share a common affected ancestor despite living in different regions of the United States (linkage disequilibrium). One Italian family is shown to have a novel dominant mutation-I290M. This is the sixth mutation identified in Thomsen's myotonia. Genotype/phenotype correlations in these four families showed that both of the dominant mutations resulted in a mild clinical picture in 90% of the patients, and no symptoms in 10% of mutation-positive patients. The EMG was the clinical feature that most closely correlated with mutation data; however, 3 of 16 (19%) mutation-positive patients tested negative by electromyography at least once, and 1 (6%) tested negative despite multiple tests. Only about half (55%) of the mutation-positive patients tested positive for percussion myotonia. Most of the clinically symptomatic individuals stated that cold temperatures and stress substantially worsened their myotonia. Our data show that dominantly inherited Thomsen's myotonia is most often a very mild disorder that shows considerable clinical heterogeneity.

Adult↗

[New electrophysiological findings on the incidence of brain involvement in clinically and neurologically asymptomatic HIV infections].

Motor (postural tremor of the outstretched hands, most rapid voluntary alternating index finger movements and rise times of most rapid voluntary isometric index finger extensions) and psychometric tests (multiple choice vocabulary test - form b, syndrome short test, the German version of the standard progressive matrices - Raven, and the psychic and somatic findings according to the AMDP-system) as well as MRI-Scans were analysed in 100 HIV-infected patients of all stages according to the actual CDC-classification, but without any central-nervous or psychic deficit. Patients with drug, alcohol or tranquilizer abuse, opportunistic, cerebral infections or fever were excluded from the study. Tremor-peak-frequencies and reaction times did not show any significant difference to an age- and sex-matched control group; the other motor parameters revealed significant slowing in the patient group and a worsening with the CDC-stages. MRI-scans of all the patients were normal. The psychometric tests did not show significant alterations on a group statistical level, especially not in the depression scales. Morphologically, the motor performances of the HIV-infected patients resembled those of patients with basal ganglia diseases (M. Huntington, M. Wilson, M. Parkinson). Correspondingly, in some cases of clinically demented HIV-positive patients, MRI-scans showed lesions in the basal ganglia. It can be concluded, that there is an early subclinical central-nervous system affection in HIV-infected patients, especially of the basal ganglia, detectable with appropriate motor function tests sometimes considerably preceeding structural deficits seen later in the course of the disease in MRI-scans.

AIDS-Related Complex↗

Enzyme immunoassay system for panel testing.

An immunoassay system based on enzyme immunoassay technology has been developed for quantitative panel testing. The system includes test card disposables, reagents, and an instrument. Patients' samples are processed semiautomatically in the instrument with minimum user intervention. The test card has multiple test areas at individual locations on a membrane solid phase so that simultaneous determinations from a single specimen are possible. Each panel also includes positive and negative reagent procedural controls. Factory-determined calibration curves for each analyte are provided in barcode form with each test kit. The reagents include a specimen dilution buffer, enzyme conjugate, and precipitogenic substrate. Up to 10 test cards at a time can be processed in random-access and continuous-access modes, with automated agitation of sample and reagents over the solid phase, temperature-controlled incubation, and membrane washing and reading, data reduction, and printout of results. The optical reader measures diffuse reflectance and features source intensity and wavelength compensation.

Chemistry, Clinical↗

The persistence of underpowered studies in psychological research: causes, consequences, and remedies.

Underpowered studies persist in the psychological literature. This article examines reasons for their persistence and the effects on efforts to create a cumulative science. The "curse of multiplicities" plays a central role in the presentation. Most psychologists realize that testing multiple hypotheses in a single study affects the Type I error rate, but corresponding implications for power have largely been ignored. The presence of multiple hypothesis tests leads to 3 different conceptualizations of power. Implications of these 3 conceptualizations are discussed from the perspective of the individual researcher and from the perspective of developing a coherent literature. Supplementing significance tests with effect size measures and confidence intervals is shown to address some but not necessarily all problems associated with multiple testing.

Humans↗

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

Brain↗

Interexaminer reliability for multiple diagnostic test regimens.

A methodology is presented for conducting interexaminer reliability studies when indication for adjustment is based on the outcomes of multiple diagnostic procedures. The adjustment decision-making process is simulated by defining multitest scores to be computed from test battery results and defining threshold values of these scores to demarcate the selection/rejection decision made by the clinician. A probability analysis of random chance agreement suggests that intermediate values of the threshold multitest scores must be used to ensure moderate agreement between observers and the viability of concordance statistics.

Chiropractic↗

The use of a measles latex reagent for the determination of measles antibodies and in a specific test for multiple sclerosis.

Measles virus antigens covalently linked to latex spheres were used for measuring measles-specific antibodies in a direct agglutination test either in microtitre plates or as a rapid slide-agglutination test. The titres were compared to that obtained by conventional assays. The measles-latex spheres were also used as the antigen for a radio-immuno assay. By incorporating a 14C-radioactive marker into the measles-latex spheres their interaction with lymphocytes from multiple sclerosis and control patients was determined. Lymphocytes from multiple sclerosis patients reacted with a higher percentage of beads at low bead/lymphocyte ratios compared with controls, whereas the reverse was found when the ratio of beads was increased.

Antibodies, Viral↗