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Depth of insertion of transpedicular vertebral screws into human vertebrae: effect upon screw-vertebra interface strength.

Improvement in the strength of the transpedicular screw-vertebra interface by increasing the depth of screw insertion may provide improved performance of spinal implants using such screws. Within human cadaveric vertebrae, we measured the failure strength of Vermont Spinal Fixator (VSF) screws under flexion or torsion loads and of Schanz screws under pull-out loads (along the screw axis). Comparisons between opposite pedicles of vertebral specimens were made at 50 vs. 80% and 80 vs. 100% of maximum available insertion depth. Mean failure strength of VSF screws at 50% depth was 75-77% (depending upon load type) of that at 80% depth; strength for screws at 100% ("to-cortex") depth was 124-154% of that at 80%. Reanalysis of the data from Lavaste shows, contrary to his conclusion, a 26% increase in strength from a 5-mm increase in screw depth of insertion. All these differences were significant (p less than 0.05) by the matched-pairs t test. Benefit from the increased strength of deeper screw placement must be balanced against possible increased operative risk. A "near-approach" x-ray view is suggested here to decrease that presumed operative risk.

Bone Screws↗

Image normalization and background subtraction in T1-201/Tc-99m parathyroid subtraction scintigraphy. Effect on lesion detection.

The authors have developed two computer algorithms for T1-201/Tc-99m parathyroid subtraction scintigraphy that was performed on patients who subsequently underwent surgical exploration of the neck. Both methods employed a region-of-interest drawn around the thyroid/parathyroid glands for image realignment. The first algorithm normalized the Tl-201 and Tc-99m images using the ratio of maximum counts over the thyroid in each image. The second computer algorithm incorporated Tl-201 image background correction and normalization by the average of the ratios of maximum counts computed over each quadrant in both images. In 10 patients with confirmed parathyroid adenomas or hyperplasia, the first method yielded a 44% sensitivity. Upon reanalysis with the second algorithm, the sensitivity improved to 100%. Subsequently, in a total of 22 patients with 30 abnormal glands analyzed with the second algorithm, a sensitivity of 80% (94% for adenoma and 62% for hyperplasia) was achieved, with a specificity of 91%, as confirmed by surgery.

Algorithms↗

A quantitative examination of the sources of speech discrimination test score variability.

Several sources of variability inherent in any speech discrimination measurement are outlined. Limitations of the use of the binomial theorem to predict intrasubject (test-retest) variability are examined. First, the underestimation of variability that is caused by the inclusion of items of different degrees of difficulty is quantified by a reanalysis of published data. Second, it is shown that variability will be larger than expected if the subject's ability is different during test and retest sessions. Fortuitously, these two deviations from the model have opposing effects on the score variability. The estimates provided by the binomial theorem are thus better than if only one effect was present. The need for a clear distinction to be maintained between inter- and intra-subject variability and the effect of list differences on test-retest variability are also discussed.

Hearing↗

Fractional absorption of ingested barium in adult humans.

A reanalysis of available data on gastrointestinal absorption of soluble barium indicates that absorption has been underestimated in most human studies. There appears to be little basis for assigning a substantially lower absorption fraction to soluble barium than to other alkaline earth elements, particularly radium, in radiation protection guidance.

Administration, Oral↗

A-bomb survivors: further evidence of late effects of early deaths.

Reanalysis of A-bomb survivor data has shown the following: a) in the high-dose (> 1 Gy) subgroups of the life span study cohort of 5-y survivors, there is a significant deficit of individuals who were < 10 y or > 50 y at the time of the bomb; and b) in the cohort on in utero children, there is a significant deficit of individuals who were < 8 wk of fetal age when exposed. This paper discusses how this selection bias has affected the perception of three effects of A-bomb radiation: marrow damage, carcinogenesis, and second-generation effects.

Age Factors↗

Fractional absorption of ingested uranium in humans.

This paper provides a review and reanalysis of data relating to gastrointestinal (GI) uptake of uranium in humans. Estimates of GI uptake of uranium in adult humans have been derived from results of three controlled experimental studies involving short-term oral intake of an elevated quantity of uranium in fluids, from a controlled balance study conducted in a metabolic research ward of a hospital, and from a variety of environmental studies in which urinary uranium could be related to total intake or total excretion of this element in the same population. For controlled studies, uptake values range from less than 0.1% to about 6% for individual subjects, with central values for different studies falling in the range 1-2.4%. Environmental studies yield central estimates in the range 0.3-3.2%. Expressed as a percentage of total intake of uranium in food and fluids, average GI uptake of uranium in adult humans appears to be about 1-1.5%. Limited intake and excretion data for environmentally exposed human subjects > or = 5 y of age do not reveal important differences with age in uranium uptake, but more definitive information is needed for children. More information is also needed to determine whether fractional uptake of uranium increases with decreasing levels of intake and whether uptake from drinking water is substantially higher than uptake from food. Data for laboratory animals indicate that fractional uptake of uranium depends strongly on the chemical form ingested and the length of time since the last intake of food.

Animals↗

Augmentation of fluoxetine's antidepressant action by pindolol: analysis of clinical, pharmacokinetic, and methodologic factors.

In a controlled trial, the beta-adrenoceptor/5-hydroxytryptamine-1A (5-HT1A) receptor antagonist pindolol accelerated and enhanced the antidepressant effect of fluoxetine. The median times to sustained response (> or = 50% reduction of baseline severity maintained until endpoint) were 19 days for fluoxetine plus pindolol (N = 55) and 29 days for fluoxetine plus placebo (N = 56) (p = 0.01). The response rate at endpoint was 16% greater in patients treated with the combination. The plasma concentration of pindolol remained stable between 3 days (first blood sampling) and 6 weeks. Mean values were approximately 26 nM, a concentration higher than the Ki of (-)pindolol for human 5-HT1A autoreceptors (11 nM). Plasma fluoxetine and norfluoxetine concentrations increased steadily until the fourth week of treatment. Fluoxetine concentrations were lower in patients receiving the combination (p = 0.043), but there was no significant relationship to the clinical response in either group. A reanalysis of the data using a survival analysis revealed that significant differences in the time to sustained response between both groups would have also been detected (1) in a 2-week trial, (2) without a placebo lead-in phase, and (3) with less frequent visits. However, the use of "response" instead of "sustained response" as measure of clinically relevant change would have greatly diminished the difference between treatment arms (p = 0.08 instead of p = 0.01). This emphasizes the need of using stringent outcome criteria in antidepressant drug trials. A comparison of the data of all sustained responders (N = 27) in the fluoxetine-plus-placebo group with the first 27 responders in the fluoxetine-plus-pindolol group (of a total of 38) revealed a highly significant difference in the time to sustained response (18 and 10 days, respectively; p = 0.0002). This indicates that the faster response in the fluoxetine-plus-pindolol group is not a result of the greater proportion of responders.

Adrenergic beta-Antagonists↗

Distorting judgments of mental health.

Labeling bias refers to subjects judging normal individuals as mentally ill as a function of diagnostically irrelevant stimuli (e.g., suggestions of mental illness made by a prestige figure). Three studies investigating the generality of the labeling bias effect are reported. Experiment 1 failed to find the effect with undergraduates, but demonstrated that these subjects can discriminate an audio tape recording of a psychiatric patient from a tape of a normal person. Experiment 2 demonstrated labeling bias in mental health service workers. Experiment 3 produced labeling bias in undergraduates by manipulating the "relevance" of the prestige figure. The data from the three studies were interpreted as indicating that, contrary to previous interpretation, professional identity is not a necessary condition for producing labeling bias. Reanalysis of the data of previous research supported the hypothesis that labeling bias is extremely general, and probably related to attractiveness of the communicator who gives the suggestion of mental illness, setting, ambiguity of desired response, and other similar variables well documented in the social psychology literature.

Attitude↗

Reliability and the discrimination of normal and pathological groups.

The authors of a recent article (Neufeld, R. W. J., and Broga, M. I. Evaluation of information sequential aspects of schizophrenic performance. II. Research strategies and methodological issues. J. Nerv. Ment. Dis., 169: 569-579, 1981) questioned the usefulness of considering reliability and other psychometric characteristics of tasks in the comparison of the pathological and normal groups on the abilities measured by the tasks. They supported their conclusion by a reanalysis of data published by Chapman and Chapman (Chapman, L.J., and Chapman, J.P. Problems in the measurement of cognitive deficit. Psychol. Bull., 79: 380-385, 1973). We contend that their conclusion was based on an inappropriate analysis of the data with a neglect of relevant psychometric principles.

Humans↗

Five-factor model of schizophrenia. Initial validation.

Schizophrenic psychopathology is heterogeneous and multidimensional. Various strategies have been developed over the past several years to assess and measure more accurately discrete domains of psychopathology. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a five-syndrome model based on a reanalysis of factor analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale. We present data on a five-factor solution that appears to best fit the psychopathological data and that is supported by three independent and comparable factor analyses; negative, positive, excitement, cognitive, and depression/anxiety domains of psychopathology give patients their individual mark. Data on internal consistency of the five factors and on initial validation using demographic and clinical variables are presented.

Adolescent↗

Seroprevalence of Helicobacter pylori infection in cystic fibrosis and its cross-reactivity with anti-pseudomonas antibodies.

BACKGROUND: The prevalence of Helicobacter pylori infection and its role in gastroduodenal disease in cystic fibrosis (CF) are controversial. Additionally, serologic determination of infection in this population may be inaccurate because of cross-reactivity with other bacterial species. The seroprevalence of H. pylori in a cohort of patients with CF and its cross-reactivity with Pseudomonas antibodies were investigated. METHODS: A research enzyme-linked immunosorbent assay (ELISA), and three commercial serologic assays (PyloriStat; BioWhittaker, Walkersville, MD, U.S.A.; Flexsure; SmithKline Diagnostics, Inc., San Jose, CA, U.S.A.; and HM-CAP; EPI, Stony Brook, NY, U.S.A.) at three independent laboratories determined the seroprevalence of anti-H. pylori IgG antibodies in 70 patients with CF. Cross-reactivity between solid-phase H. pylori antigens and Pseudomonas antibodies was ascertained by a competitive inhibition assay, preadsorbing sera of patients with CF with whole cell proteins from different Pseudomonas species, and serum reanalysis by each assay. Western blot analysis before and after adsorption was performed to identify potential cross-reactive antigens. RESULTS: The research ELISA, Flexsure, Pyloristat, and HM-CAP initially showed H. pylori seropositivity of 47%, 28%, 24%, and 37%, respectively. Postadsorption seropositivity declined to 8%, 0%, 0%, and 15%, respectively. All patients with research ELISA true-positive results were confirmed endoscopically to have H. pylori infection. Western blot analysis showed a 31-kDa H. pylori protein with antigenic epitopes common to both bacterial species. CONCLUSIONS: Cross-reactivity between solid-phase H. pylori antigens and anti-Pseudomonas antibodies occurs in patients with CF. A high index of suspicion should be assumed in evaluating results of serologic H. pylori tests in this population. Preadsorption of CF sera with Pseudomonas proteins should be used in serologic testing.

Adolescent↗

Biomechanical predictor of commotio cordis in high-speed chest impact.

BACKGROUND: Commotio cordis is a term used to describe cases of blunt thoracic impact causing fatality without gross structural damage of the heart and internal organs. Death is attributed to ventricular fibrillation or cardiac arrhythmia aggravated by traumatic apnea. The biomechanical response related to the risk of commotio cordis has not been determined. METHODS: Reanalysis of previously published experimental data was performed to determine which biomechanical parameter predicts the occurrence of commotio cordis. Logistic regression was used to determine the risk for commotio cordis with the level of chest compression, rate of chest deformation, and viscous criterion. RESULTS: By using only cases without serious tissue injury (Abbreviated Injury Scale score < 4), viscous criterion was the best predictor of commotio cordis or ventricular fibrillation (chi2 = 7.69, p = 0.006). It was also the best predictor of heart rupture (chi2 = 13.19,p = 0.0003) and severe cardiac injury with Abbreviated Injury Scale score > or = 4 (chi2 = 25.03, p = 0.0001). CONCLUSION: Based on this in-depth analysis, the viscous criterion is the relevant biomechanical response to assess the risk of commotio cordis and more severe thoracic injury in high-speed blunt impact.

Abbreviated Injury Scale↗

Assessment of blood lactate: practical evaluation of the Biosen 5030 lactate analyzer.

PURPOSE: The aim of this study was to assess the validity and reliability of the Biosen 5030 lactate analyzer compared with a YSI 2300 lactate analyzer and a Kodak Ektachem DTII in a practical laboratory study context. METHODS: To assess validity, 144 triplicate capillarized blood samples, across a range of values, were analyzed using the three analyzers. To assess reliability a further 665 samples were repeat analyzed. Temporal stability was determined by the reanalysis of resting and maximal exercise blood samples, after a period of storage ranging from 7 to 20 h, at room temperature. To measure inter- and intra-investigator reliability, 20 resting samples were taken from three different subjects by different investigators and a coefficient of variation was determined. RESULTS: There were strong relationships between the Biosen, the YSI (r2 = 0.97), and the Kodak Ektachem (r2 = 0.91). An analysis of Biosen compared with YSI revealed a positive bias of 0.37 mmol x L(-1) (95% limits of agreement, -0.85 to 1.59 mmol x L(-1)). The test-retest reliability correlation was significant (r2 = 0.99, P < 0.05), but a paired t-test revealed a small (0.03 mmol x L(-1), P < 0.05) significant difference. The coefficient of variation from the three investigators across the 20 samples ranged from 1.3 to 3%. Blood lactate concentration in resting blood samples did significantly increase in value (0.2 mmol x L(-1), P < 0.05) after 7-h exposure to the air, whereas there was no change in maximal exercise blood lactate values after 20-h exposure to the air. CONCLUSIONS: In a practical context, the Biosen 5030 lactate analyzer was comparable to the other analyzers giving fast reliable measures of blood lactate concentrations over the full range of values, which remained stable over extended periods at room temperature.

Bias↗

The epidemiology of brain arteriovenous malformations.

OBJECTIVE: Common estimates of the prevalence rate for pial arteriovenous malformations (AVMs) of the brain vary widely, and their accuracy is questionable. Our objective was to critically review the original sources from which these rates were derived and to establish best estimates for both the incidence and prevalence of the disease. METHODS: We reviewed all of the relevant original literature: autopsy series, the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage and related analyses, and other population-based studies. We also modeled the confidence intervals of estimates for a process of low prevalence such as AVMs. RESULTS: Many of the prevalence estimates (500-600/100,000 population) were based on autopsy data, a source that is inherently biased. Other estimates (140/100,000 population) originated from an inappropriate analysis of data from the Cooperative Study. The most reliable information comes from a population-based study of Olmsted County, MN, but prevalence data specific to AVMs was not found in that study. CONCLUSION: The estimates for AVM prevalence that are published in the medical literature are unfounded. Because of the rarity of the disease and the existence of asymptomatic patients, establishing a true prevalence rate is not feasible. Owing to variation in the detection rate of asymptomatic AVMs, the most reliable estimate for the occurrence of the disease is the detection rate for symptomatic lesions: 0.94 per 100,000 person-years (95% confidence interval, 0.57-1.30/100,000 person-years). This figure is derived from a single population-based study, but it is supported by a reanalysis of other data sources. The prevalence of detected, active (at risk) AVM disease is unknown, but it can be inferred from incidence data to be lower than 10.3 per 100,000 population.

Autopsy↗

Inter-observer agreement in the reporting of 99Tcm-DMSA renal studies.

The early identification of renal cortical scarring secondary to urinary reflux and/or renal infection is important in the management of patients with recurrent disease. Scintigraphic imaging of the renal cortex using 99Tcm-dimercaptosuccinic acid (DMSA) is often considered the standard method for the diagnosis of renal scars in both adults and children. Consistent reporting of 99Tcm-DMSA is nevertheless essential in ensuring that the clinician can act on the data reported. In this study, seven experienced observers were asked to report, independently, 99Tcm-DMSA data sets from 32 patients. The observers were asked to note the presence of a space occupying lesion or of a renal cortical scar(s) and to conclude if the kidney was normal or abnormal. There was marked variation in the number of renal cortical scars reported, the total number of scars seen and whether or not the kidney was normal or abnormal. After peer review of all data, consensus and referenced criteria were arrived at for a reanalysis of data. All scans were reread by the observers. There was some improvement in the concordant reporting of kidneys with renal scars (51 vs 61%) and whether or not the kidney was normal or abnormal (53 vs 63%). However, this was not statistically significant (at a level of P < 0.05). This study demonstrated significant inter-observer variation regarding the reporting of 99Tcm-DMSA studies. A consensus with agreed guidelines for data interpretation did not significantly affect this apparent lack of consistency of reporting.

Adolescent↗

Behavioral clusters and coronary heart disease risk.

The purpose of the present study was to empirically identify individuals who differed in their patterns of components derived from the structured interview (SI), and to evaluate whether individuals characterized by the different patterns varied in terms of their risk for coronary heart disease (CHD). The present study represents a reanalysis of data from the Western Collaborative Group Study in which components of Type A were individually related to risk for CHD. Subgroups of individuals who differed in the patterns of their component scores were identified by means of cluster analytic techniques and were found to vary in their risk of CHD. As expected, a pattern of characteristics in which hostility was salient was found to be predictive of CHD. Moreover, another pattern of characteristics that appears to reflect pressured, controlling, socially dominant behavior in which hostility was not salient also was found to be predictive of CHD. Further, two patterns of characteristics were identified that were unrelated to CHD risk. Finally, two patterns of characteristics were identified that were related to reduced risk of CHD. Overall, these results suggest that future research should investigate variables in addition to hostility in regard to risk for and protection from CHD.

Adult↗

Zenilman's anomaly reconsidered: fallible reports, ceteris paribus, and other hypotheses.

BACKGROUND AND OBJECTIVES: In the January-February, 1995 issue of Sexually Transmitted Diseases, Zenilman and colleagues reported a null association between incident sexually transmitted diseases (STDs) and self-reported condom use. That anomalous finding generated a flurry of letters to the editor, some of which were quite heated. This article reconsiders the Zenilman team's results. STUDY DESIGN: New statistical analyses were conducted to test two hypotheses that sought to account for the null association: (1) deviation from study protocol, and (2) differential risks of acquiring an incident STD among segments of the study population that varied by reported level of condom use. RESULTS: No support was found for hypotheses concerning deviation from study protocol and differential risk of acquiring an incident STD by level of condom use. Indeed, for respondents who reported multiple sexual partners, the analyses found increased rates of infection among those who reported more consistent condom use. CONCLUSIONS: Two of the most promising hypotheses for explaining Zenilman's anomalous findings are unsupported by reanalysis of the available empirical evidence. It is still possible that respondents who reported that they used condoms consistently differed from self-reported nonusers or inconsistent users in some way that altered their risk of acquiring an STD and thus obscured the protective effects of properly used condoms. Nonetheless, as Zenilman and others suggest, fallibility in self-reports of condom use remains the primary suspect as the cause of these anomalous results. Such fallibility may be particularly pronounced when self-reported behavioral data are collected in contexts that include strong educational campaigns or other norm-setting interventions.

Bias↗

Hormonal therapy for metastatic prostate cancer: issues of timing and total androgen ablation.

This review summarize results of hormonal management in patients with metastatic prostate cancer in terms of both timing and amount of androgen blockade. The standard of delayed hormonal therapy resulted from data of the Veterans Administration Cooperative Urologic Research Group showing high toxicity in patients treated with estrogen therapy. Reanalysis of those data using cancer-specific deaths showed improved cancer-specific survival with early hormonal therapy. A large and growing body of clinical data also suggests a superior benefit to early hormonal therapy. The concept of total androgen (adrenal and testicular) ablation was supported by reports that show a survival advantage using a combined blockade over luteinizing hormone-releasing hormone agonist alone. A National Cancer Institute study showed particularly impressive disease-free and overall survival in a subset of patients with low volume disease and good performance status. However, caution should be exercise in view of differing Canadian and European data. This review provides guidelines for treatment, but ultimately the timing and amount of androgen deprivation must be tailored to the individual patient. Ongoing and future prospective studies hold the promise of answers to these difficult and unresolved questions.

Adrenalectomy↗