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Serum estradiol level and oocyte number in predicting severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a relatively common and potentially life-threatening complication of ovarian stimulation, the pathogenesis of which remains unclear. To clarify the predictive values of serum estradiol levels and oocyte number in severe OHSS, and to investigate the impact of high serum estradiol levels on pregnancy outcome, we retrospectively analyzed clinical data from 431 cycles of ovarian stimulation for assisted reproduction performed from 1993 through 1995. Receiver operating characteristic plots were used to estimate the predictive power of the measured variables. The overall frequency of severe OHSS was 5.5%. Using a serum estradiol level of 3,600 pg/mL as the minimum cut-off value, the sensitivity was 58%, with a specificity of 92%, a positive predictive value of 29%, and a negative predictive value of 97%. The predictive power was similar when a cut-off point of 20 oocytes retrieved was used. The two criteria together gave a sensitivity of 33%, a specificity of 92%, a positive predictive value of 40%, and a negative predictive value of 98%. One of seven oocyte donors developed severe OHSS. The pregnancy rate was higher in patients with severe OHSS than in patients who did not develop this syndrome (73.9% vs 32.5%) but the pregnancy outcomes were not significantly different. We conclude that elevated estradiol concentrations and oocyte number appear to be helpful in predicting severe OHSS, but neither parameter by itself is predictive. This syndrome is rare in the absence of luteal hCG support, either exogenous or pregnancy-derived; when it occurs, there are usually extremely high preovulatory estradiol concentrations and numerous oocytes retrieved. High serum estradiol levels are unlikely to have adverse effects on pregnancy outcome in patients with severe OHSS.

Adult↗

Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397].

INTRODUCTION: Pro-adrenomedullin (proADM) is helpful for individual risk assessment and outcome prediction in sepsis. A major cause of sepsis is community-acquired pneumonia (CAP). The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in CAP. METHODS: Data from 302 patients admitted to the emergency department with CAP were included in a prospective observational study. Procalcitonin, C-reactive protein levels, leukocyte count, clinical variables and the pneumonia severity index (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany). RESULTS: ProADM levels, in contrast to C-reactive protein and leukocyte count, increased with increasing severity of CAP, classified according to the PSI score (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on admission were significantly higher compared to levels in survivors (2.1 (1.5 to 3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for proADM was 0.76 (95% confidence interval (CI) 0.71-0.81), which was significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI (0.73, p = 0.54). A clinical model including the PSI and proADM increased the prognostic accuracy to predict failure compared to a model relying on the PSI alone (AUC, 0.77 (0.70 to 0.84), p = 0.03). CONCLUSION: ProADM, as a novel biomarker, is a useful tool for the risk stratification of patients with CAP.

Adrenomedullin↗

Prenatal sonographic chest and lung measurements for predicting severe pulmonary hypoplasia in left-sided congenital diaphragmatic hernia.

To assess the prenatal evaluation of lung hypoplasia in congenital diaphragmatic hernia (CDH), we attempted to measure the right lung area/thorax area ratio (rLT ratio) in normal fetuses and in seven cases of left-sided CDH. In addition, we analyzed early neonatal blood gas data, which were compared with the prenatal evaluation. The rLT ratio was significantly (p<0.05) higher in normal fetuses (0.27+/-0.02) than in CDH (0.14+/-0.18). The values of PaO(2), arterial-alveolar oxygen difference (A-aDO(2)) and oxygenation index (OI) showed no significant relationship with the rLT ratio in CDH at the early neonatal period. Three infants with CDH survived and showed significant higher values of rLT ratio compared with those in nonsurvived infants (p<0.05). All of the rLT ratios in nonsurvived infants were <0.11. PaO(2) at the early neonatal period was significantly (p<0.05) higher, and both A-aDO(2) and OI were significantly (p<0.05) lower in survived infants than in nonsurvived infants. These results indicated that prenatal evaluation of rLT ratio is useful to predict the severity of lung hypoplasia in infants with left-sided CDH, and blood gas analysis at early neonatal period is also useful to predict the neonatal outcome.

Blood Gas Analysis↗

Age at symptom onset predicts severity of motor impairment and clinical outcome of glutaric acidemia type 1.

OBJECTIVES: In patients with glutaric acidemia type 1 (GAI), biochemical and molecular markers fail to predict the course of individual patients; therefore we sought to identify nonbiochemical variables that correlate with severity of motor deficits or overall clinical outcome. STUDY DESIGN: Archival data was collected from 42 published articles describing 115 patients with GA1. A forward, stepwise, multiple regression analysis was used to find predictors for outcome. RESULTS: Analyses show that in patients who did not have a precipitating illness before the first appearance of motor symptoms, the age at onset was significantly associated with the severity of motor impairments and overall clinical outcome. In patients who had a precipitating illness, the age at onset did not predict the outcome. In both groups of patients, basal ganglia degeneration, enlargement of spaces containing cerebrospinal fluid, and white matter abnormalities were indicative of a poorer prognosis. Treatment given after the appearance of symptoms was not associated with a better clinical outcome or fewer motor deficits. CONCLUSION: Because the age at symptom onset can significantly predict the severity of motor deficits and the overall outcome, it is important to identify patients with GA1 as early as possible. Several studies suggest that presymptomatic treatment may prevent or postpone the onset of symptoms.

Age of Onset↗

Influenza-specific ELISA IgA and IgG predict severity of influenza disease in subjects prescreened with hemagglutination inhibition.

Four influenza A challenge studies were performed over a period of three years using the same dose of one virus pool. The first three studies were conducted two influenza seasons apart from the last study. In all four studies only subjects with screening hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8 in sera were accepted as study subjects. The rate of infection after influenza challenge was 96% (25 of 26) in the first three studies, and only 73% (8 of 11) in the last study (P less than 0.04). The rate of influenza illness in the first three studies was 62% (16 of 26), and only 9% (1 of 11) in the last study (all subjects: P = 0.003; infected subjects: P = 0.01). Even though screening HAI titers were comparable between groups, prechallenge serum influenza-specific IgG titers correlated inversely with respiratory symptoms (P = 0.04). Prechallenge nasal wash influenza-specific IgA titers were lower in subjects who developed influenza illness (P = 0.03). Prechallenge influenza-specific nasal wash ELISA-IgA titers and serum ELISA-IgG titers predicted influenza severity in patients prescreened by HAI during influenza challenge studies.

Adolescent↗

Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism.

BACKGROUND: Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. METHODS: Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring supplementation. RESULTS: Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P =.02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P =.03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P <.001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. CONCLUSIONS: Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation.

Adult↗

Chlamydia trachomatis antibody titres by enzyme-linked immunosorbent assay are useful in predicting severity of adnexal adhesion.

The aim of this study was to investigate the relationship between chlamydia infection and adnexal adhesion. A total of 131 infertile women who were otherwise asymptomatic underwent chlamydia antibody testing and laparoscopy. These women had additional infertility factors. Serum concentration of anti-Chlamydia trachomatis immunoglobulins G and A were determined prospectively by means of an enzyme-linked immunosorbent assay (ELISA). Results were compared with the tubal patency and severity of adnexal adhesion. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of anti-C.trachomatis antibody titres for the presence of adnexal adhesion were calculated. Patients who were positive for chlamydia antibody had a significantly higher incidence of tubal occlusion than those who were negative (47.1 versus 25.0%). Adnexal adhesion scores were significantly higher in the patients who were positive for chlamydia antibody than those in patients who were negative (17.1 versus 8.5). Adnexal adhesion scores were significantly correlated with anti-chlamydia antibody titre by ELISA [immunoglobulin (Ig) G: r = 0.60, Ig A: r = 0.61]. As the antibody titre by ELISA rose, the specificity, positive predictive value and the positive likelihood ratio all increased. In conclusion, C.trachomatis antibody testing is a simple and inexpensive means of predicting pelvic damage and laparoscopic examination may be recommended for patients with high anti-C.trachomatis antibody titres by ELISA.

Adnexal Diseases↗

Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin.

Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 microg/dL; UFC, 2000 microg/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.

Adolescent↗

Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol.

This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity.

Adult↗

The impact-acceleration model of head injury: injury severity predicts motor and cognitive performance after trauma.

This study examines neuropsychological dysfunction after varying severities of the Impact Acceleration Model of diffuse traumatic brain injury. Adult rats (340 g-400 g) were divided into five groups, and exposed to varying degrees of Impact Acceleration Injury (1 m, 2 m, 2.1 m/500 g and second insult). After injury, animals were allowed to recover; acute neurological reflexes, beam walk score, beam balance score, inclined plane score, and Morris Water Maze score were then assessed at multiple time points. Injury of all severities caused significant motor and cognitive deficits. With milder injuries these effects were transient; however, with more severe injuries no recovery in function was seen. The addition of hypoxia and hypotension made a moderate injury worse than a severe injury. The acute neurological reflexes, the beam balance test and the inclined plane test distinguished between the more severely injured groups, but were affected less by mild injury. The beam walk test was sensitive to mild injury, but appeared unable to distinguish between the severe groups. The Morris Water Maze was sensitive for all injury groups, but appeared to adopt a different response profile with secondary insult. This study has for the first time characterized the degree of motor and cognitive deficits in rodents exposed to differing severities of Impact Acceleration Injury. These data confirm that the tests considered, and the Injury Model used, provide a useful system for the consideration of potential therapies which might ameliorate neuropsychological deficits in diffuse brain injury.

Acceleration↗

Predicting severe angiographic coronary artery disease using computerization of clinical and exercise test data.

Currently the standard exercise test is shifting from being a tool for the cardiologist to utilization by the nonspecialist. This change could be facilitated by computerization similar to the interpretation programs available for the resting ECG. Therefore, we sought to determine if computerization of both exercise ECG measurements and prediction equations can substitute for visual analysis performed by cardiologists to predict which patients have severe angiographic coronary artery disease. We performed a retrospective analysis of consecutive patients referred for evaluation of possible or known coronary artery disease who underwent both exercise testing with digital recording of their exercise ECGs and coronary angiography at two university-affiliated Veteran's Affairs medical centers and a Hungarian hospital. There were 2,385 consecutive male patients with complete data who had exercise tests between 1987 and 1997. Measurements included clinical and exercise test data, and visual interpretation of the ECG paper tracings and > 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized ECG measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were only able to correctly classify two or three more patients out of 100 tested than ECG measurements alone. beta-Blockers had no effect on test characteristics while ST depression on the resting ECG decreased specificity. By setting probability limits using the scores from the equations, the population was divided into high-, intermediate-, and low-probability groups. A strategy using further testing in the intermediate group resulted in 86% sensitivity and 85% specificity for identifying patients with severe coronary disease. We conclude that computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist and computerized scores only minimally improved the discriminatory power of the test. However, using these scores in a stratification algorithm allows the nonspecialist physician to improve the discriminatory characteristics of the standard exercise test even when resting ST depression is present. Computerization permitted accurate identification of patients with severe coronary disease who require referral.

Coronary Angiography↗

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Adult↗

Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation.

Only a subset of hepatitis C virus (HCV)-infected patients develop progressive hepatic fibrosis after liver transplantation (LT). Hepatic stellate cell (HSC) activation is a pivotal step in hepatic fibrosis and precedes clinically apparent fibrosis. We determined whether early HSC activation, measured in 4-month protocol post-LT biopsies, is predictive of subsequent development of more histologically severe recurrence of HCV. Early (4 month) post-LT HSC activation, as measured by alpha-smooth muscle actin (alpha-SMA) staining, was determined in liver biopsies from recipients with severe (fibrosis score > or = 2, n = 13) and with mild (fibrosis score of 0, n = 13) recurrence of HCV at one-year post-LT. Immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) was used to generate HSC activation scores (regional and total). Total HSC activation scores at 4 months were similar in patients with severe and mild HCV recurrence (3.9 +/- 2.0 vs. 2.7 +/- 2.2, P = 0.2). Regional HSC activation, assessed as parenchymal (zones 1, 2, and 3) or mesenchymal (portal tracts and fibrous septa), was different between the study groups, with higher mesenchymal scores predictive of progression. No patients in the mild recurrence group had detectable mesenchymal alpha-SMA staining vs. 46% (6/13) of patients with severe recurrence (P < 0.01). Mesenchymal activation of HSC had a specificity and positive predictive value of 100% for development of progressive fibrosis in liver allografts of patients with hepatitis C. In conclusion, early activation of mesenchymal HSCs is a marker for progressive fibrosis in patients with hepatitis C post-LT and may help select patients who would benefit from HCV or HSC-targeted therapy.

Actins↗

The Hong Kong criteria and severity prediction in acute pancreatitis.

Fan et al. have reported that a blood urea > 7.4 mmol/L and/or glucose > 11 mmol/L at the time of admission to hospital detect severe acute pancreatitis with a sensitivity of 76% and specificity of 80.3%. We have retrospectively applied these criteria to a consecutive series of 125 patients with a diagnosis of acute pancreatitis within the West of Scotland. Utilizing the Hong Kong criteria we were only able to detect severe attacks of acute pancreatitis with a sensitivity of 33% (specificity of 83%). By lowering the concentration of urea and glucose employed to > or = 4.9 mmol/L and > or = 7.5 mmol/L, respectively, and utilizing peak concentrations recorded during the first 48 h rather than values measured at the time of admission, we were able to increase the sensitivity to 65% while reducing the specificity to 77%. Even after modification, the Hong Kong criteria were a less effective means of identifying severe attacks of acute pancreatitis than either the Glasgow scoring system (sensitivity 78% and specificity 86%) or clinical assessment at 48 h (sensitivity 82% and specificity 96%).

Acute Disease↗

Does matrix metalloproteinase activity predict severity of acute pancreatitis?

BACKGROUND: Matrix metalloproteinases (MMP) modulate end-organ complications of acute pancreatitis, but the correlation between increased MMP production and histological severity of disease remains unclear. We examined the role of MMP and pancreas histology on experimental acute pancreatitis. METHODS: Forty male Wistar albino rats were subjected to cerulein-induced pancreatitis (8, 16, 24 and 32 h groups) or sham treatment. The animals were killed at different time points and pancreatic tissues were harvested to assess MMP (1, 2 and 9) activity and inflammatory changes. RESULTS: Compared with other groups, 8 h group had decreased tissue MMP-1 concentrations. MMP-9 concentrations were lower in 24-h and 32-h groups, as were histological severity scores. MMP-2 activity did not differ among groups. Pancreatitis was prominent in 8-h, 16-h and 24-h groups by means of histology. CONCLUSION: Induction of pancreatitis by cerulein altered pancreatic MMP levels in the early phase of inflammation. Inhibition of MMP-2 and MMP-9 paralleled histological scores. Therefore, MMP may have a predictive value to assess histological severity.

Acute Disease↗

Evidence that health attributions and symptom severity predict insight in schizophrenia.

Although a relationship between insight and symptomatology in schizophrenia has been repeatedly demonstrated, the influence of psychological variables such as coping mechanisms and attributional style is less clear. We evaluated health attributions, subjective resources for coping, symptomatology, general cognitive functioning, and insight among 38 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area. Health attributions accounted for a significant amount of insight even after symptom severity was accounted for and together predicted 32% of variation in insight scores. This study emphasizes the multifactorial nature of insight and the importance of psychological variables in addition to symptomatology.

Adaptation, Psychological↗

Lasting anxiogenic effects of feline predator stress in mice: sex differences in vulnerability to stress and predicting severity of anxiogenic response from the stress experience.

Previous work in male Swiss Webster (CFW) mice demonstrated a long lasting effect of predator stress on risk assessment in the elevated plus maze (EPM). Most severe effects (increases in risk assessment) were seen following a brief unprotected exposure to a cat. Lesser effects were produced by a brief exposure of mice to the cat exposure room without a cat in the room (room stress). This graded response is analogous to the covariation of symptom severity and severity of the precipitating stressor in posttraumatic stress disorder (PTSD). The present study extended these findings to another strain of mice, C57/BL6, and a broader range of tests of anxiety-like behavior, including EPM, acoustic startle response and light/dark box test. Sex was introduced as a variable to investigate if females might be more susceptible to the effects of stressors than males, as has been suggested in human PTSD. Graded and lasting (7 days) effects of a 10 min exposure to a cat (predator stress) or to the cat exposure room only (room stress) were observed on lighted chamber avoidance in the light/dark box. Room stress was without effect on startle responses, but predator stress enhanced peak startle amplitudes measured in the light or in the dark. There was no evidence of light-enhancement of startle in C57 mice. Female mice were more susceptible to the effects of predator and room stress, depending on the measure. Females only responded to cat exposure with a lasting increase in average startle amplitude. This was due to an increased and more prolonged multipeak response to startle after the first and maximal peak startle response. In addition, in females, room and predator stress were equally anxiogenic in measures of open arm avoidance in the EPM. In contrast, room stress was without effect on open arm avoidance in males, but cat exposure was as anxiogenic in males as it was in females. These findings suggest EPM anxiety in females is affected more by the milder stress of room exposure. Severity of effects of predator stress on anxiety-like behaviors in EPM and startle were well predicted (60% of the variance) by measures of cat behavior and probability of mouse defensive response to particular cat behaviors during the cat exposure. Finally, factor analysis indicated that different tests of anxiety-like behavior may be measuring different and independent aspects of mouse affect. Moreover, stressors had no lasting effects on sugar solution consumption. Implications of these findings for modeling PTSD and using transgenic strains of mice to study lasting effects of stress on affect are discussed.

Analysis of Variance↗