Predictor Odds Ratio Research Articles

SNOT-22 scores after 6 months of aspirin therapy are predictive of long-term quality of life in AERD

Background: Aspirin exacerbated respiratory disease (AERD) is an inflammatory condition that consists of eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions to cyclooxygenase-1 inhibitors. Aspirin therapy after aspirin desensitization (ATAD) is the most extensively studied treatment paradigm for AERD. Objective: The objective was to identify which time point of ATAD was most predictive of long-term outcomes as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). Methods: A retrospective chart review was conducted of patients at a single institution who underwent endoscopic sinus surgery, followed by ATAD, and had remained on ATAD for 2 consecutive years. SNOT-22 scores were recorded at predesensitization as well as at the 3-, 6-, 12-, and 24-month postdesensitization time points. The patients were separated into two cohorts at each of the data collection time points based on whether their SNOT-22 scores were < 20 (responders) or ≥ 20 (nonresponders). Responder status was compared between each time point and at 24-month postdesensitization. The odds ratios (OR) were then calculated between the two groups at each of the following time points: postsurgery/predesensitization, and 3-, 6-, and 12-month postdesensitization. Results: There were 70 patients who met the inclusion criteria of having 24-month postdesensitization SNOT-22 scores available. Responder status at 6 months after surgery had the most predictive OR 16.5 (95% confidence interval, 3.71-73.44) for long-term outcomes at 24 months. Conclusion: The SNOT-22 scores after 6 months of ATAD showed the greatest predictive value for long-term quality-of-life outcomes and, therefore, poor 6-month SNOT-22 scores could serve as a basis for consideration of alternative therapies.

Mammographic breast density and breast cancer risk in the Saudi population: a case-control study using visual and automated methods.

This study aims to establish risk of breast cancer based on breast density among Saudi women and to compare cancer prediction using different breast density methods. 1140 pseudonymised screening mammograms from Saudi females were retrospectively collected. Breast density was assessed using Breast Imaging Reporting and Data System (BI-RADS) density categories and visual analogue scale (VAS) of 285 cases and 855 controls matched on age and body mass index. In a subset of 160 cases and 480 controls density was estimated by two automated methods, Volpara Density™ and predicted VAS (pVAS). Odds ratios (ORs) between the highest and second categories in BI-RADS and Volpara density grades, and highest vs lowest quartiles in VAS, pVAS and Volpara Density™, were estimated using conditional logistic regression. For BI-RADS, the OR was 6.69 (95% CI 2.79-16.06) in the highest vs second category and OR = 4.78 (95% CI 3.01-7.58) in the highest vs lowest quartile for VAS. In the subset, VAS was the strongest predictor OR = 7.54 (95% CI 3.86-14.74), followed by pVAS using raw images OR = 5.38 (95% CI 2.68-10.77) and Volpara Density ™ OR = 3.55, (95% CI 1.86-6.75) for highest vs lowest quartiles. The matched concordance index for VAS was 0.70 (95% CI 0.65-0.75) demonstrating better discrimination between cases and controls than all other methods. Increased mammographic density was strongly associated with risk of breast cancer among Saudi women. Radiologists' visual assessment of breast density is superior to automated methods. However, pVAS and Volpara Density ™ also significantly predicted breast cancer risk based on breast density. Our study established an association between breast density and breast cancer in a Saudi population and compared the performance of automated methods. This provides a stepping-stone towards personalised screening using automated breast density methods.

Appropriateness and affordability of prescriptions to diabetic patients attending a tertiary hospital in Eastern Uganda: A retrospective cross-sectional study.

BackgroundIrrational prescription of drugs can lead to high cost of treatment thus limiting access to essential medicines. We assessed the affordability and appropriateness of prescriptions written for diabetic patients in Eastern Uganda.MethodsWe collected secondary data from the health management information system registers of patients who attended the outpatient medical clinic at Mbale regional referral hospital from January 2019 to December 2019. The average cost of the prescriptions was calculated and adjusted odds ratios for predictors for unaffordability estimated using logistic regression. Computed scores for indicators of rational drug prescription were used to assess the extent of rational prescribing.ResultsThe median cost per prescription was USD 11.34 (IQR 8.1, 20.2). Majority of the diabetic patients (n = 2462; 94.3%, 95% CI: 93.3–95.1%) could not afford the prescribed drugs. Predictors for unaffordability were if a prescription contained: ≥ 4 medicines (AOR = 12.45; 95% CI: 3.9–39.7); an injectable (AOR = 5.47; 95%CI: 1.47–20.32) and a diagnosis of diabetes mellitus with other comorbidities (AOR = 3.36; 95%CI: 1.95–5.78). Having no antidiabetic drug prescribed was protective for non-affordability (AOR = 0.38; 95%CI: 0.24–0.61). The average number of drugs per prescription was 2.8. The percentage prescription of drugs by generic name and from the essential medicine and health supplies list of Uganda were (6160/7461; 82.6%, 96% CI: 81.7%-83.4%) and (6092/7461; 81.7%, 95% CI: 80.8%-82.5%) respectively against WHO standard of 100%.ConclusionThe majority of diabetic patients (94.3%) in Eastern Uganda cannot afford to buy prescribed medicines. The government should therefore ensure that essential medicines are readily accessible in public health facilities.

Drug safety in hospitalized patients with tuberculosis: Drug interactions and adverse drug effects.

Hospitalized patients with tuberculosis (TB) are prescribed with drugs having high risk of potential drug-drug interactions (pDDIs) and adverse drug effects (ADEs). To explore the adverse effects of anti-tuberculosis (anti-TB) drugs and the prevalence and predictors of pDDIs in hospitalized patients with TB. Clinical profiles of 436TB patients were reviewed for adverse effects induced by anti-TB drugs and screened for pDDIs using Micromedex-DrugReax. Prevalence and severity levels of pDDIs were reported. Odds ratios for predictors were calculated using logistic regression analysis. Of total 436 patients, adverse effects of anti-TB drugs were found in 36%. ADEs were highly prevalent in patients with high doses of anti-TB drugs. Hepatotoxicity, neuropathy, insomnia, arthralgia, psychosis, hematological alterations, skin rashes, red color stool, diplopia, and photophobia were the identified ADEs. All drugs types- and anti-TB drugs-pDDIs were reported in 78.2% and 55.7%, respectively. Major-pDDIs of anti-TB drugs were identified in 55.5%. Total 1090 anti-TB drugs pDDIs were found, among them, 55.6% were of major- and 40.5% were of moderate-severity. Significant association was observed for the pDDIs with≥7 prescribed medicines (P<0.001). Potential adverse outcomes of the most frequent interactions were hepatotoxicity, decreased drug's effectiveness, QT-interval prolongation, nephrotoxicity, and gastrointestinal ulceration. Patients with TB present with a considerable number of clinically important pDDIs and ADEs (particularly hepatotoxicity). TB patients should be monitored for adverse effects of anti-TB drugs. Attention should be given to major-pDDIs. Patients more at risk to interactions should be identified and monitored for related adverse outcomes.

Fertility desire concordance and contraceptive use among couples living with HIV in northern Nigeria

Objectives We aimed to determine the concordance between own and perceived partner fertility intentions and identify predictors of contraceptive use among couples receiving antiretroviral therapy in Kano, Nigeria. Methods A structured, validated questionnaire was used to interview 399 married men and women receiving antiretroviral therapy. Adjusted odds ratios for predictors of contraceptive use were derived from multivariate logistic regression models. Results Most couples (68.9%) had concordant fertility intentions. Only 10.0% of couples had discordant fertility intentions. Among 232 couples (58.1%) at least one partner used contraception. Male condoms were used by 45.9% of couples (n = 183). Female methods were used by 175 couples (43.9%). Contraceptive use was significantly higher in participants who were older (≥30 years), better educated (secondary or post-secondary), had a higher monthly income (NGN ≥30,000), longer marriage duration (≥5 years), at least one living child, >1 year of antiretroviral treatment, and who were living with a serodiscordant partner and in circumstances where the decision on contraception was made by the female partner or jointly by both partners (all p < 0.05). Contraceptive use was significantly lower in participants who had not been sexually active in the last 6 months, where both partners wanted more children, and in situations lacking spousal communication about family planning (all p < 0.05). Conclusion One in 10 couples had discordant fertility intentions. Contraceptive use was suboptimal and was predicted by age, education, income, length of marriage, number of children, duration of antiretroviral therapy, partner’s serostatus, sexual activity, fertility intention, spousal communication and the contraceptive decision-maker. Our findings highlight the need for spousal communication, joint contraceptive decision making and the integration of reproductive health services with antiretroviral therapy services.

Abstract TP61: The Predictive Ability of Aspects vs Ct Perfusion for Large-vessel Occlusions Less Than 6 Hours

Background: While CT perfusion (CTP) has become invaluable in the selection of acute ischemic stroke patients for endovascular therapy (EVT) ≥6 hours of symptom onset, there continues to be uncertainty in its role within 6 hours. Hypothesis: CTP will select patients for EVT better than ASPECTS - as RAPID software can provide quantitative volumetric thresholds, while ASPECTS is subject to interpersonal variability. Methods: Patients over 18 years old with last known well (LKW) time to imaging less than 6 hours, and a confirmed large-vessel occlusion at the ICA, M1 or M2 were reviewed retrospectively. ASPECTS ratings were assessed by two blinded neuroradiologists. A diagnostic odds ratio (OR) was calculated by dichotomizing ASPECTS ≥6 vs &lt;6, and comparing to the modified Rankin score (mRS) ≤0-2 vs &gt;2. A separate diagnostic OR was calculated for CTP by dichotomizing the infarct core (cerebral blood flow (CBF) &lt;30%) ≤50 ml vs &gt;50 ml. Results: Ninety-six subjects were evaluated. Mean age was 65.4±14, 42% female, presenting with a mean NIHSS 16.4±8, 65% were treated with IV tPA, and mean clot retrieval was 5.3±2 hours for those who underwent EVT (70/96). The mean ASPECTS was 7.6±2, and mean infarct core (CBF&lt;30%) of 34.4±50. Inter-rater reliability for ASPECTS grading was ICC=0.797 (95%CI 0.378-0.932). ASPECTS and CTP were found to be in agreement in 83.3% (80/96) of cases on whether or not to pursue EVT. In incongruent cases, in which ASPECTS was favorable but CTP was unfavorable - 54% (6/11) had mRS between 4-6, and similarly 50% (8/16) had a poor mRS when CTP was favorable but ASPECTS was unfavorable. In general, both ASPECTS and CTP poorly correlated with the utility-mRS (r = 0.14 and r = -0.15 respectively) when controlling for age, sex, time (LKW-to-CTP), and treatment (EVT± tPA, tpA alone, or none). Overall, diagnostic OR for prediction of a good outcome (mRS 0-2) for ASPECTS was 1.5 (95% CI 0.4-4.5) vs 3.4 for CTP (95% CI of 1.2-9.2), p=0.29. When accounting for treatment subtype, the diagnostic OR was 1.2 (0.4-3.6) for ASPECTS vs 2.9 for CTP (1.1-8.1), p=0.24. Conclusion: Approximately 1:6 patients will have incongruent results between ASPECTS and CTP. ASPECTS was not significantly better than CTP in cases &lt;6 hours. In fact, a trend for better predictive ability was seen with CTP.

Seizure self-prediction in a randomized controlled trial of stress management.

Using electronic diaries as part of a randomized controlled trial of stress reduction for epilepsy, we evaluated factors associated with successful seizure self-prediction. Adults with medication-resistant focal epilepsy were recruited from 3 centers and randomized to treatment with progressive muscle relaxation or control focused attention. An 8-week baseline was followed by 12 weeks of double-blind treatment. Twice daily, participants rated the likelihood of a seizure in the next 24 hours on a 5-point scale from very unlikely to almost certain, along with mood, premonitory symptoms, stress ratings, and seizure counts. We analyzed the association of mood, premonitory symptoms, stress, and circadian influences on seizure self-prediction. Sixty-four participants completed the trial (3,126 seizures). Diary entry adherence was >82%. Participant self-prediction was associated with seizure occurrence at 6, 12, and 24 hours (p < 0.0001). Odds ratio (OR) of seizure prediction increased systematically with participants' prediction of seizure likelihood (p < 0.0001, all levels of prediction and all time intervals). For the 12-hour prediction window, median specificity for seizure prediction was 0.94 and negative predictive value 0.94; median sensitivity was 0.10 and positive predictive value 0.13. A subset of 13 participants (20% of sample) met criteria for good predictors (median OR for seizure prediction 5.25). Mood, stress, premonitory symptoms, seizure time, and randomized group were not associated with seizure occurrence. In this prospective study, participants' prediction of a high probability of seizure was significantly associated with subsequent seizure occurrence within 24 hours. Future studies should focus on understanding factors that drive self-prediction. NCT01444183.

Potential drug-drug interactions among pneumonia patients: do these matter in clinical perspectives?

BackgroundPneumonia patients are usually hospitalized due to severe nature of the disease or for the management of comorbid illnesses or associated symptoms. Such patients are prescribed with multiple medications which increase the likelihood of potential drug-drug interactions (pDDIs). Therefore, in this study the prevalence, levels (severity and documentation), predictors (risk factors), and clinical relevance of pDDIs among inpatients diagnosed with pneumonia have been investigated.MethodsClinical records of 431 hospitalized patients with pneumonia were checked for pDDIs using drug interactions screening software (Micromedex-DrugReax). Odds-ratios for predictors were calculated using logistic regression analysis. Clinical relevance of pDDIs was assessed by evaluation of patients’ clinical profiles for potential adverse outcomes of the most frequent pDDIs. Abnormal patients’ signs/symptoms and laboratory investigations indicating adverse outcomes of interactions were reported.ResultsOf total 431 profiles, pDDIs were reported in 73.1%. Almost half of the profiles were having major-pDDIs (53.8%). Total number of pDDIs were 1318, of which 606 were moderate- and 572 were major-pDDIs. Patient’s profiles identified with the most frequent interactions were presented with signs, symptoms, and abnormalities in labs indicating decrease therapeutic response, electrolyte abnormalities, hypoglycemia, bleeding, hepatotoxicity, and hypertension. These adverse events were more prevalent in patients taking higher doses of the interacting drugs as compared to lower doses. Logistic regression analysis revealed significant association for major-pDDIs with 6–10 prescribed medicines (OR = 26.1; p = 0.002), > 10 prescribed medicines (OR = 144; p < 0.001), and tuberculosis (OR = 8.2; p = 0.004).ConclusionsPDDIs are highly prevalent in patients with pneumonia. Most frequent and clinically important pDDIs need particular attention. Polypharmacy and tuberculosis increase the risk of pDDIs. Identifying patients more at risk to pDDIs and careful monitoring of pertinent signs/symptoms and laboratory investigations are important measures to reduce pDDIs and their related adverse consequences.

Drug-Drug Interactions in Hepatitis Patients: Do these Interactions Matter in Clinical Perspectives?

Introduction and aim. Hepatitis patients usually present with comorbidities and polypharmacy which increases risk of potential drug-drug interactions (pDDIs). We explored frequency, levels, predictors, and clinical relevance of pDDIs in hospitalized hepatitis patients. Methods. Retrospective cohort study was used. Clinical profiles of 413 hepatitis patients were reviewed for pDDIs using Micromedex-DrugReax. Frequency, levels and clinical relevance of pDDIs were reported. Logistic regression analysis was used to calculate odds-ratios for predictors. Results. Of total 413 patients, pDDIs were reported in 55.2%. Major-pDDIs were found in 35% patients. Total 660 pDDIs were identified, of which, 304 (46%) were of major-severity and 299 (45%) of moderate-severity. Patient’s profiles of top-10 major-pDDIs were presented with signs/symptoms such as fever, hepatomegaly, anorexia, jaundice, hypertension, tachycardia, bradycardia, &amp; pedal edema; and abnormalities in labs such as electrolytes-level, alanine aminotransferase, blood urea nitrogen, bilirubin-level, &amp; serum creatinine. Significant association was observed for the presence of pDDIs with &gt;9 prescribed medicines (p &lt; 0.001), hospitalization of &gt;5 days (p = 0.03), and stroke as comorbidity (p = 0.05). Moreover, odds of exposure to major-pDDIs were significantly higher in patients taking &gt;9 prescribed medicines (p &lt; 0.001), hospitalization of &gt;5 days (p = 0.002), and stroke as comorbidity (p = 0.002). Conclusion. We observed hepatitis patients present with a considerable number of clinically relevant pDDIs. Attention should be given to widespread major-pDDIs and their potential adverse outcomes. Clinically relevant parameters, such as labs and signs/symptoms should be monitored particularly in high risk patients having polypharmacy, prolong hospitalization, and stroke as comorbidity.

Preferential traits for breeding Nguni cattle in low-input in-situ conservation production systems

A cross-sectional study was conducted in communal and small-scale Nguni cattle enterprises to determine preferential traits for improvement under low-input cattle breeding programs. Forty-one farmers participated in ranking six specific traits of breeding bulls and cows. Kruskal-Wallis test and ordinal logistic regression were used to determine mean ranks of traits and odds ratios of predictors (enterprise ownership, gender, farmer age, education level, agriculture training) on specified trait ranks, respectively. Preferential traits for breeding bulls were in the order; aggression and mating behaviour (1.86), tick and disease resistance (1.90), body condition score (2.69), scrotal circumference (4.52), body size and conformation (4.71) and coat colour (5.02). For breeding cows,preferential order were; tick and disease resistance (1.55), reproductive efficiency (2.02), body condition score (3.14), body size and conformation (4.21), coat colour (4.74) and milk yield (5.31). Less old farmers (< 50 years) and those from communal enterprises preferred bull coat colour more than scrotal circumference. Farmers with primary education and those with formal agriculture training had the least odds ratio estimates on the poorly ranked bull coat colour. The informally trained farmers, older age group (> 50 years), females and those from small-scale enterprises had odds ratio estimates less than one for the sixth ranked milk yield in Nguni cows. It was concluded that trait preference in breeding bulls and cows is significantly influenced by socio-economic and demographic factors. It is recommended to consider farmer preferences in trait selection and designing communal breeding programs.

An Elevated Maternal Plasma Soluble fms-Like Tyrosine Kinase-1 to Placental Growth Factor Ratio at Midtrimester Is a Useful Predictor for Preeclampsia

Background. To assess the ability of mid-trimester sFlt-1/PlGF ratio for prediction of preeclampsia in two different Arabic populations. Methods. This study measured levels of sFlt-1, PlGF, and sFlt-1/PlGF ratio at midtrimester in 83 patients who developed preeclampsia with contemporary 250 matched controls. Results. Women subsequently developed preeclampsia had significantly lower PlGF levels and higher sFlt-1 and sFlt-1/PlGF ratio levels than women with normal pregnancies (P < 0.0001 for all). Women who with preterm preeclampsia had significantly higher sFlt-1 and sFlt-1/PlGF ratio than term preeclamptic women (P = 0.01, 0.003, resp.). A cutoff value of 3198 pg/mL for sFlt-1 was able to predict preeclampsia with sensitivity, specificity, and accuracy of 88%, 83.6%, and 84.7%, respectively, with odds ratio (OR) 37.2 [95% confidence interval (CI) 17.7–78.1]. PIGF at cutoff value of 138 pg/mL was able to predict preeclampsia with sensitivity, specificity, and accuracy of 85.5%, 77.2%, and 79.3%, respectively, with OR 20 [95% CI, 10.2–39.5]. The sFlt-1/PIGF ratio at cutoff value of 24.5 was able to predict preeclampsia with sensitivity, specificity, and accuracy of 91.6%, 86.4%, and 87.7%, respectively with OR 67 [95% CI, 29.3–162.1]. Conclusion. Midtrimester sFlt-1/PlGF ratio displayed the highest sensitivity, specificity, accuracy, and OR for prediction of preeclampsia, demonstrating that it may stipulate more effective prediction of preeclampsia development than individual factor assay.

P5-13-17: Multigene Signature Assays in Patients with Early-Stage Breast Cancer (ESBC) Receiving Neoadjuvant Chemotherapy: An NCI-Funded Systematic Review and Evidence Summary of Predictive Performance.

Abstract Background: A comprehensive literature search and evidence synthesis of multigene signatures predictive of response to systemic chemotherapy in patients with breast cancer was initiated as a part of an NCI-funded program on Comparative Effectiveness Research. Methods: Validation studies were sought of multigene signatures for prediction of chemotherapy response (favorable vs unfavorable) in ESBC patient cohorts different from those used for signature development. Pooled estimates [±95% CI] of assay performance for predicting clinical outcome included sensitivity, specificity, likelihood ratio, predictive value (PV) and predictive odds ratio (POR) utilizing mixed effects models based on the method of Mantel-Haenszel. Exploratory metaregression analyses on log (POR) were also performed. Studies were classified by validation type including cell lines to patients, independent internal sample, random split sample, or external validation. Evidence for publication bias was assessed by Egger's regression intercept and Begg and Mazumdar's rank correction. Results: Dual-blind review of abstracts identified 33 studies of neoadjuvant chemotherapy response of which 29 stratified treatment response by signature classifier category. Classifier development was based on tumor response prediction in 20 studies, prognosis in 5, and molecular classification in 4. The Table shows assay performance measures overall and by study validation type. Assay performance based on the POR was positively associated with overall study quality (P=.015) and journal impact factor (P=.020). However, strong evidence for publication bias was observed based on both regression intercept (P&amp;lt;.001) and rank correlation (P=.005). No significant differences in assay performance were noted for assays originally developed for response prediction (POR=5.3), prognosis (POR=6.6) or molecular classification (P=6.9) (P=.770). Conclusions: While assay performance in predicting response to neoadjuvant chemotherapy based on multigene classifiers is encouraging, a compelling need exists for greater methodologic rigor and standardization of reporting. The predictive performance of multigene assay signatures varies with the type of validation sample utilized with external validation providing the most conservative estimates. No differences were seen for assays developed for prediction, prognosis or molecular classification. Considerable evidence for publication bias exists reflecting a paucity of smaller negative studies. The clinical validity of genomic response prediction assays should be evaluated in patient cohorts independent of those utilized for signature development. The clinical utility of these assays must then be further assessed in comparative effectiveness studies compared to commonly utilized clinical and laboratory measures. Funding: NCI: UC2CA14041-01 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-17.

Association of an apolipoprotein E polymorphism with circulating cholesterols and hypertension: a meta-based Mendelian randomization analysis

Prospective studies have reported that circulating cholesterol abnormalities are predictive of hypertension. As a test of the causal influence of circulating cholesterols on hypertension, we used a meta-based Mendelian randomization analysis to determine whether the apolipoprotein E (ApoE) gene polymorphism ɛ2/ɛ3/ɛ4 related to cholesterol changes is associated with hypertension. Data were available from 17 study populations, encompassing 2896 hypertensive patients and 2898 controls. A random effects model was applied irrespective of a between-study heterogeneity, and publication bias was examined using a funnel plot and Egger's test. An overall comparison of the ApoE gene alleles ɛ4 with ɛ3 yielded a significant 81% increased risk for hypertension (95% confidence interval (95% CI): 1.41-2.32; P<0.0005). Restricting the analysis to populations of Asian descent resulted in a 1.87-times higher likelihood of developing hypertension (95% CI: 1.41-2.32; P<0.0005). Compared with ɛ3 carriers, ɛ4 allele carriers had significantly higher levels of total cholesterol (standardized mean difference (SMD)=0.39; 95% CI: 0.2-0.57; P<0.0005) and low-density lipoprotein cholesterol (SMD=0.43; 95% CI: 0.23-0.64; P<0.0005). The predicted odds ratio (OR) for a 1 mmol l(-1) increase in total cholesterol was 4.58 (95% CI: 1.83-67.21) when all qualified studies were included and 4.98 (95% CI: 1.94-76.36) for Asian-descent populations. Similarly, the predicted OR for a 1-mmol l(-1) increase of low-density lipoprotein cholesterol was 3.97 (95% CI: 1.71-43.48) in all populations and 4.29 (95% CI: 1.81-43.38) in Asian-descent populations. Taken together, our findings suggest a casual influence of high circulating total cholesterol and low-density lipoprotein cholesterol levels on the development of hypertension.

Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden

IntroductionAutoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and in those with rheumatoid arthritis, suggesting a gradual development of these diseases. Therefore, we sought to identify autoantibodies in a northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.MethodsThe register of patients fulfilling the American College of Rheumatology criteria for SLE and with a given date of the onset of symptoms was coanalysed with the register of the Medical Biobank, Umeå, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Medical Biobank register (Umeå, Sweden). Antibodies against anti-Sjögren's syndrome antigen A (Ro/SSA; 52 and 60 kDa), anti-Sjögren's syndrome antigen B, anti-Smith antibody, ribonucleoprotein, scleroderma, anti-histidyl-tRNA synthetase antibody, double-stranded DNA (dsDNA), centromere protein B and histones were analysed using the AtheNA Multi-Lyte ANA II Plus Test System on a Bio-Plex Array Reader (Luminex200). Antinuclear antibodies test II (ANA II) results were analysed using indirect immunofluorescence on human epidermal 2 cells at a sample dilution of 1:100.ResultsAutoantibodies against nuclear antigens were detected a mean (±SD) of 5.6 ± 4.7 years before the onset of symptoms and 8.7 ± 5.6 years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA II, with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies, both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratios (ORs) for predicting disease were 18.13 for anti-dsDNA (95% confidence interval (95% CI), 3.58 to 91.84) and 11.5 (95% CI, 4.54 to 28.87) for ANA. Anti-Ro/SSA antibodies appeared first at a mean of 6.6 ± 2.5 years prior to symptom onset. The mean number of autoantibodies in prediseased individuals was 1.4, and after disease onset it was 3.1 (P < 0.0005). The time predating disease was shorter and the number of autoantibodies was greater in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations as the presenting symptoms.ConclusionsAutoantibodies against nuclear antigens were detected in individuals who developed SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR being for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

Effective Prediction of Preeclampsia by a Combined Ratio of Angiogenesis-related Factors

OBJECTIVE Imbalance between angiogenesis-related factors is closely related to the development of preeclampsia. The objective was to estimate the most effective and accurate predictive biomarker among levels and ratios of angiogenesis-related factors, including soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin, placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1), in women who subsequently developed preeclampsia. METHODS A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-beta1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women. RESULTS Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-beta1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-beta1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-beta1) were significantly higher than in normotensive women (P<.001) and even greater in severe preeclampsia with preterm delivery compared with mild preeclampsia with term delivery (P<.05). At equivalent sensitivity (85%), the false-positive rate was 45% for sFlt-1, 41% for soluble endoglin, 33% for sFlt-1/PlGF, 21% for soluble endoglin/TGF-beta1, and 10% for the combined ratio. After adjusting for potential confounding factors, the risks for developing preeclampsia were as follows: odds ratio (OR) 6.9 [95% confidence interval 2.3-20.7] for sFlt-1 level, 7.1 [2.3-21.7] for soluble endoglin level, 6.8 [2.4-19.4] for sFlt-1/PlGF, 38.8 [9.8-154.3] for soluble endoglin/TGF-beta1, and 74.8 [17.6-316.7] for the combined ratio. CONCLUSION The combined ratio of angiogenesis-related factors showed the lowest false-positive rate and the highest OR for prediction of preeclampsia, indicating that it may provide more effective prediction of development of preeclampsia. LEVEL OF EVIDENCE II.

Effective Prediction of Preeclampsia by a Combined Ratio of Angiogenesis-Related Factors

Imbalance between angiogenesis-related factors is closely related to the development of preeclampsia. The objective was to estimate the most effective and accurate predictive biomarker among levels and ratios of angiogenesis-related factors, including soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin, placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1), in women who subsequently developed preeclampsia. A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-beta1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women. Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-beta1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-beta1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-beta1) were significantly higher than in normotensive women (P<.001) and even greater in severe preeclampsia with preterm delivery compared with mild preeclampsia with term delivery (P<.05). At equivalent sensitivity (85%), the false-positive rate was 45% for sFlt-1, 41% for soluble endoglin, 33% for sFlt-1/PlGF, 21% for soluble endoglin/TGF-beta1, and 10% for the combined ratio. After adjusting for potential confounding factors, the risks for developing preeclampsia were as follows: odds ratio (OR) 6.9 [95% confidence interval 2.3-20.7] for sFlt-1 level, 7.1 [2.3-21.7] for soluble endoglin level, 6.8 [2.4-19.4] for sFlt-1/PlGF, 38.8 [9.8-154.3] for soluble endoglin/TGF-beta1, and 74.8 [17.6-316.7] for the combined ratio. The combined ratio of angiogenesis-related factors showed the lowest false-positive rate and the highest OR for prediction of preeclampsia, indicating that it may provide more effective prediction of development of preeclampsia. II.

The EXCITE Trial: Predicting a Clinically Meaningful Motor Activity Log Outcome

Background and Objective . This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. Methods. A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Results. Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Conclusions. Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT.

VALIDATION OF MATERNAL SELF-REPORTED PROXIMITY TO AGRICULTURAL CROPS IN A CASE-CONTROL STUDY OF NEURAL TUBE DEFECTS

ISEE-470 Abstract: There is a suspicion among epidemiologists that self-reported perinatal exposures to chemicals or pollutant sources in case-control studies of birth defects may be inaccurate due to misreporting among mothers of malformed infants, non-malformed controls, or both. We tested this suspicion in a study of neural-tube defects delivered in California in 1987-1988. In that study, mothers were asked about proximity to agricultural crops and pesticide applications. We employed historical land-use survey maps to validate self-reported residential proximity within 0.25 mile of agricultural crops. Using map-based proximity to geocoded residences as our gold-standard, we compared case-control odds ratios (ORs) calculated for 1) self-reported and 2) map-based proximity to any crops and to non-permanent field crops, orchards, and vineyards and compared the sensitivity and specificity of maternal reports for cases and controls by geographic region and maternal demographic characteristics. Logistic regression was used to derive adjusted ORs for predictors of underreporting and overreporting of proximity to crops. The OR for self-reported proximity to any crops appeared to be positively biased (1.63; 95% confidence interval (CI): 1.09, 2.45), compared to the OR based on map-based proximity (1.17; 95% CI: 0.79, 1.72). This difference appeared to be primarily a function of control mothers underreporting proximity to crops. That is, sensitivity of self-reported proximity was greater for cases (66.7%) than controls (50.4%), while specificity was slightly lower in cases (87.7% vs. 89.5%). Similar trends were observed for proximity to specific crop types, except for vineyards. Underreporting appeared to be negatively associated with NTD cases (OR: 0.56; 95% CI: 0.29, 1.10) versus controls and rural residents (OR: 0.51; 95% CI: 0.25, 1.06) versus urban residents. Mothers employed during pregnancy (OR: 2.25; 95% CI: 1.14, 4.46) were more likely to underreport than unemployed women. Overreporting of proximity was positively associated with rural residence (OR: 1.88; 95% CI: 0.95, 3.73) and residence in Central California (OR: 2.21; 95% CI: 1.08, 4.53). In addition, we observed a positive dose-response relationship for overreporting with maternal educational level and maternal gestational cigarette smoking. These results suggest differential reporting of proximity to crops between case and control mothers as well as an influence from geographic region and some maternal demographic characteristics on reporting accuracy.

Short-term and long-term fracture prediction by bone mass measurements: a prospective study.

Prospective and cross-sectional studies have demonstrated that bone mass predicts fracture risk. However, most prospective studies have been limited to a few years of follow-up. We investigated the long-term associations of bone mass with vertebral fractures using longitudinal data collected from more than 500 postmenopausal Japanese-American women in the Hawaii Osteoporosis Study. New vertebral fractures were identified during an average of 2.7 years between 1992 and 1995. Short-term fracture prediction was evaluated using bone mass (spine, calcaneus, distal radius, and proximal radius) measured at the beginning of follow-up. Long-term prediction was evaluated using bone mass measured before the follow-up period (11 years earlier for nonspine bone mass and 8 years earlier for spine). All four bone mass measurements were significant predictors of vertebral fractures identified during the subsequent 2.7 years (short-term prediction), with odds ratios (ORs) ranging from 1.5 to 1.9. The ORs for long-term prediction were slightly lower in magnitude, but the confidence intervals overlapped the short-term ORs considerably, suggesting that both long-term and short-term associations are similar in magnitude. Furthermore, cross-sectional analyses based on bone mass measurements performed at the end of follow-up (after fractures had occurred) yielded results similar to those based on prospective data (bone mass measured prior to fractures), suggesting that the relatively quick and inexpensive cross-sectional studies are useful for preliminary evaluations of new bone mass measurement techniques. The results suggest that bone mass measurements made up to 11 years earlier can predict vertebral fractures almost as well as measurements made more recently.