Multivariate Forward Stepwise Regression Research Articles

Comparing Symptoms of Major Depression in Youth with Confirmed Versus Suspected Bipolar Disorder.

Background: While numerous studies have compared symptoms of major depressive episodes (MDEs) associated with bipolar disorder (BD; i.e., bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression), little is known about this topic in youth. We compared MDE symptoms in youth with BD with youth with suspected BD who have similar clinical and familial characteristics aside from having BD. Methods: MDE symptoms based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) Depression Rating Scale items for the most severe past episode were compared in youth, ages 13-21 years, with BD (n = 208) versus suspected BD (n = 165). Diagnoses were confirmed via semistructured interviews. Symptoms with between-group differences (p < 0.05) in univariate analyses were evaluated in a multivariate forward stepwise regression. All analyses controlled for age and sex. Results: Youth with BD had significantly higher (more severe) ratings on depressed mood (p = 0.001, η2 = 0.05), irritability (p = 0.037, η2 = 0.02), anhedonia (p = 0.004, η2 = 0.04), negative self-image (p < 0.001, η2 = 0.07), hopelessness (p = 0.04, η2 = 0.02), fatigue (p = 0.001, η2 = 0.05), hypersomnia (p = 0.001, η2 = 0.05), suicidal ideation (p = 0.04, η2 = 0.02), and recurrent thoughts of death (p < 0.001, η2 = 0.05). In regression analyses, the only symptom that remained significant in the BD group was depressed mood (p = 0.002). Conclusions: These findings demonstrate greater severity of depressive symptoms in youth with BD versus MDD across mood, and cognitive and neurovegetative symptom domains. These differences are especially noteworthy given that the MDD group was highly similar to the BD group, aside from BD diagnosis. Present findings emphasize the need for novel treatment approaches to bipolar depression in youth, and for studies examining potential mechanisms underlying the increased severity of bipolar depression.

Can a clinical assessment predict the functional status progression in patients with femoroacetabular impingement syndrome?

BackgroundFemoroacetabular impingement syndrome (FAIS) is a hip joint motion-related clinical disorder with a triad of symptoms, clinical signs, and imaging findings. However, scientific evidence is still unclear regarding the best treatment for FAIS. ObjectivesTo assess the value of a physical therapy evaluation in predicting the progression of functional status over the subsequent years in patients with FAIS who are candidates for hip arthroscopy surgery. MethodsIn this case-series study, patients with FAIS, candidates for hip arthroscopy surgery, underwent a standard physical therapy evaluation. Baseline data were collected between 2013 and 2019. In 2020/2021, the patients’ functional status was assessed through the International Hip Outcome Tool (iHOT-33). Functional status progression was calculated as the difference between the follow-up and baseline iHOT-33 scores. A multivariate forward stepwise regression analysis was conducted to explore the relationship between baseline characteristics and the functional status progression. ResultsFrom 353 patients who completed the baseline assessment, 145 completed the iHOT-33 follow-up. The mean (±SD) follow-up time was 58.7 (27.2) months (minimum 12 and maximum 103 months). The iHOT-33 scores increased 20.7 (21.8) points on average, ranging from -39.8 to 76.9 points. Among the 15 potential predictive factors assessed in this study, only baseline iHOT-33 score (β -0.44; -0.061, -0.27), femoral version (β 9.03; 1.36, 16.71), and body mass index (β -0.99; -1.98, -0.01) had the ability to predict the functional status progression. ConclusionPatients with a lower baseline iHOT-33 score, lower body mass index, and normal femoral version were more likely to increase their functional status after a minimum of one year of follow-up.

Development of a modified frailty index for adult spinal deformities independent of functional changes following surgical correction: a true baseline risk assessment tool.

To develop a simplified, modified frailty index for adult spinal deformity (ASD) patients dependent on objective clinical factors. ASD patients with baseline (BL) and 2-year (2Y) follow-up were included. Factors with the largest R2 value derived from multivariate forward stepwise regression were including in the modified ASD-FI (clin-ASD-FI). Factors included in the clin-ASD-FI were regressed against mortality, extended length of hospital stay (LOS, > 8days), revisions, major complications and weights for the clin-ASD-FI were calculated via Beta/Sullivan. Total clin-ASD-FI score was created with a score from 0 to 1. Linear regression correlated clin-ASD-FI with ASD-FI scores and published cutoffs for the ASD-FI were used to create the new frailty cutoffs: not frail (NF: < 0.11), frail (F: 0.11-0.21) and severely frail (SF: > 0.21). Binary logistic regression assessed odds of complication or reop for frail patients. Five hundred thirty-one ASD patients (59.5yrs, 79.5% F) were included. The final model had a R2 of 0.681, and significant factors were: < 18.5 or > 30 BMI (weight: 0.0625 out of 1), cardiac disease (0.125), disability employment status (0.3125), diabetes mellitus (0.0625), hypertension (0.0625), osteoporosis (0.125), blood clot (0.1875), and bowel incontinence (0.0625). These factors calculated the score from 0 to 1, with a mean cohort score of 0.13 ± 0.14. Breakdown by clin-ASD-FI score: 51.8% NF, 28.1% F, 20.2% SF. Increasing frailty severity was associated with longer LOS (NF: 7.0, F: 8.3, SF: 9.2days; P < 0.001). Frailty independently predicted occurrence of any complication (OR: 9.357 [2.20-39.76], P = 0.002) and reop (OR: 2.79 [0.662-11.72], P = 0.162). Utilizing an existing ASD frailty index, we proposed a modified version eliminating the patient-reported components. This index is a true assessment of physiologic status, and represents a superior risk factor assessment compared to other tools for both primary and revision spinal deformity surgery as a result of its immutability with surgery, lack of subjectivity, and ease of use.

The Relationship Between Diet, Gut Microbiota, and Serum Metabolome of South Asian Infants at 1 Year

BackgroundDiet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person’s long-term health. Infant development can be affected by diet, which also interacts with the developing gut microbiota. ObjectivesThis study aimed to explore the associations between diet, the gut microbiota, and the serum metabolome of 1-y-old infants with the overarching goal of identifying serum biomarkers of diet and/or the gut microbiota. MethodsWe derived dietary patterns of 1-y-old infants (n = 182) participating in the Canadian South Asian Birth Cohort (START) study. We compared gut microbiota α-diversity and β-diversity and taxa relative abundance from 16S rRNA gene profiles with dietary patterns (PERMANOVA, Envfit) and investigated diet–serum metabolite associations using a multivariate analysis (partial least squares–discriminant analysis) and univariate analysis (t test). We explored the effect of nondietary factors on diet–serum metabolite relationships by incorporating diet, the gut microbiota, and maternal, perinatal, and infant characteristics in a multivariable forward stepwise regression. We replicated this analysis in White European infants, from the CHILD Cohort Study (n = 81). ResultsA dietary pattern characterized by formula consumption and negatively associated with breastfeeding most strongly predicted variation in the gut microbiota (R2 = 0.109) and serum metabolome (R2 = 0.547). Breastfed participants showed higher abundance of microbes from the genera Bifidobacterium (3.29 log2-fold) and Lactobacillus (7.93 log2-fold) and higher median concentrations of the metabolites S-methylcysteine (1.38 μM) and tryptophan betaine (0.43 μM) than nonbreastfed participants. Formula consuming infants showed higher median concentrations of branched-chain/aromatic amino acids (average 48.3 μM) than non–formula-consuming infants. ConclusionsFormula consumption and breastfeeding most strongly predicted the serum metabolites of 1-y-old infants, even when the gut microbiota, solid food consumption, and other covariates were considered.

P216 RENAL RESISTANCE INDEX IS INDEPENDENTLY ASSOCIATED WITH THE WORSENING OF RENAL FUNCTION AFTER CORONARY ANGIOGRAPHY

Abstract Background The term Cardiorenal Syndrome (CS) has been recently introduced to indicate the close relationship between cardiovascular and renal diseases, which are able to reciprocally influence the each other progression. In this setting the renal resistance index (RRI) has been demonstrated to be a useful parameter able to detect patients at higher risk of CS. However, there are no data about its role in predicting worsening of renal function (WRF) mediated by the intravascular administration of contrast. Aim of the Study To evaluate the role of RRI in predicting WRF after coronary angiography. METHODS We enrolled 115 patients (mean age 64 years, 73% males, 84% hypertensive, 43% diabetic, 30% with acute coronary syndrome, 21% affected by chronic heart failure, CHF, with a mean left ventricular ejection fraction, LVEF, of 51±11) with suspected coronary artery disease, stable angina, or acute coronary syndromes who have been referred for coronary angiography (with or without pre–existing renal impairment). All patients underwent medical examination, electrocardiogram, echocardiographic and chemical evaluation, and renal arterial echo–color Doppler used to calculate RRI. WRF was defined as an increase of creatinine &amp;gt;0.3 mg/dl and of at least 25% from baseline 24–48 hours after coronary angiography. Results After coronary angiography, 14 (12%) of the enrolled patients showed WRF. As shown in the Table, at univariate regression analysis baseline RRI was associated with WRF as well as age, peripheral artery disease, CHF, atrial fibrillation, NYHA class, LVEF, mitral regurgitation (MR), central venous pressure (CVP), tricuspid regurgitation (TR), estimated glomerular filtration rate (GFR). In a multivariate forward stepwise regression model, including all univariate predictors, history of CHF, high CVP and RRI were the only parameters significantly associated with WRF. Conclusion Our findings demonstrate that in patients undergoing coronary angiography, history of CHF, high CVP and RRI are independent predictors of WRF. RRI, but not GFR, is independently associated with WRF probably because providing additional relevant information about cardiorenal pathophysiological factors reflecting the hemodynamic status and kidney flow reserve.

Influence of Risky Pathoanatomy and Demographic Factors on Clinical Outcomes After Isolated Medial Patellofemoral Ligament Reconstruction: A Regression Analysis

Background: Multiple studies have demonstrated that a number of demographic and pathoanatomic characteristics are associated with patellofemoral instability, recurrence of instability, and less satisfactory results following medial patellofemoral ligament reconstruction (MPFL-R). Despite the growing volume of research, the relationship of risk factors to patient-reported outcome after MPFL-R is unclear. Purpose: To determine if certain pathoanatomic and demographic factors predict disease-specific quality-of-life outcome after isolated MPFL-R for symptomatic patellofemoral instability. Study Design: Cohort study; Level of evidence, 3. Methods: The study analyzed 224 isolated MPFL-Rs. Demographic data were collected, including age at first dislocation, sex, and presence of bilateral instability. Pathoanatomic risk factors included the presence of high-grade trochlear dysplasia, tibial tubercle–trochlear groove (TT-TG) distance, patella alta ratio, Beighton score, and patellar tilt. Other factors included femoral tunnel position accuracy and WARPS/STAID score. Descriptive analyses were conducted, followed by calculation of individual Spearman rank correlation coefficients for the predictor variables versus the Banff Patellofemoral Instability Instrument (BPII) scores. A multivariable regression with stepwise selection was employed to establish the final model predicting BPII score, with all significant variables for alpha ≤ .05 included in the final model. Results: The cohort of 224 patients included 66 (29.5%) males and 158 (70.5%) females, with a mean age of 24.1 years and a mean body mass index of 23.9 kg/m2. The mean age of first patellar dislocation was 15.7 years, and 41.4% of patients had bilateral instability. Pathoanatomic variables within the cohort included the following: high-grade trochlear dysplasia = 41%; mean TT-TG = 14.6 mm, with 16.8% of patients demonstrating a TT-TG ≥18 mm; mean Caton-Deschamps ratio = 1.09, with 22% of patients demonstrating a ratio ≥1.2; and positive Beighton score = 37.5%. The mean BPII score at postoperative 2 years was 67.1 out of 100. A stepwise elimination in the regression model demonstrated no statistically significant 3- or 2-way relationships. Assessment of individual variables indicated that bilateral symptoms (P = .004), higher age at first dislocation (P = .024), and femoral tunnel position >10 mm from the Schöttle point (P = .042) were statistically significant predictors of lower quality-of-life scores. The R2 value for the regression analysis model was 0.07. Conclusion: In this large cohort of patients undergoing isolated MPFL-R for symptomatic lateral patellofemoral instability, a multivariable forward stepwise regression demonstrated that bilateral symptoms, femoral tunnel position, and age at first dislocation were statistically significant predictors of lower postoperative BPII scores. No anatomic risk factors were predictive of quality-of-life outcome score 2 years after MPFL-R surgery. The R2 value indicated that there were many other important contributing factors affecting BPII outcome scores than those explored in this study.

The Utrecht Score: A novel histopathological scoring system to assess the prognosis of dogs with cortisol-secreting adrenocortical tumours.

A cortisol‐secreting adrenocortical tumour (ACT) is the cause of naturally occurring canine hypercortisolism in approximately 15% to 20% of cases. The differentiation between an adrenocortical adenoma and carcinoma is usually based on histopathology. However, histopathological parameters have never been linked to the dogs' survival. Moreover, in human medicine the inter‐observer variability of some histopathological parameters that are used for ACTs is high. The objective of this study was to establish a reliable and easy‐to‐use histopathological scoring system for cortisol‐secreting ACTs that can assess the prognosis of dogs after adrenalectomy. Cortisol‐secreting ACTs of 50 dogs, collected between 2002 and 2015, were included in this study. Twenty histopathological features were assessed by one veterinary pathologist and one resident in veterinary pathology. In addition, the Ki67 proliferation index was assessed by two observers. Only parameters with intra‐ and inter‐observer agreement scores (intra‐class correlation or Cohen's kappa coefficient) of ≥0.40 were included in survival analyses. Use of multivariate forward stepwise regression analysis with associated hazard ratios led us to a scoring system which we call the Utrecht score: the Ki67 proliferation index, +4 if more than 33% of the tumour cells have clear/vacuolated cytoplasm and + 3 if necrosis is present. Using cut‐off values of 6 and 11, we could distinguish three groups that had significantly shorter survival times with increasing Utrecht scores. We conclude that the Utrecht score can be used to assess the prognosis of dogs with cortisol‐secreting ACTs after adrenalectomy, which can help to select high‐risk dogs that might benefit from adjuvant treatment or additional monitoring.

Formula for the prediction of apnea / hypopnea index in children with obstructive sleep apnea without polysomnography according to the clinical parameters: Is it reliable?

Purpose of the studyThe aim of the study was to propose “the risk formula” for obstructive sleep apnea in children according to the general and local clinical parameters and findings relevant for obstructive sleep apnea (OSA) severity. The unmet need for this formula arises from the economic burden of polysomnography (device, staff, training, special sleep centers, etc) as the golden standard for the diagnostics. Materials and methods usedThe study was performed from January 2013 until January 2016 in the Sleep Center, Department for Neuroscience, School of Medicine of the University of Split, Department of Pediatrics, University Hospital Split, Croatia and ENT Dept. University Hospital in Split, Croatia. Inclusion criteria were: age > two years, AHI >1 diagnosed by polysomnography. Exclusion criteria were: chronic lung disease, active tonsillitis/pharyngitis at the time of the physical exam and syndromes that affect breathing. All polysomnograms were scored by a qualified sleep technologist and interpreted by two board certified sleep physicians independently. Age, sex, BMI, Mallampati score, tonsillar size and adenoids size were recorded. All statistical calculations were performed using SPSS 20. ResultsIn total 60 children were included in the study. The median of age was 5 years (range 2–9). There were 19 (32%) girls and 41 (68%) boys.Of all evaluated predictors, there were statistically significant differences in the values of AHI among children with different modified Mallampati score (χ2 = 28.2; p < 0.001), different size of tonsils (χ2 = 25.3; p < 0.001) and different size of adenoids (z = 2.7; p = 0,006) in univariate regression analysis. Strong positive association of AHI with modified Mallampati score (standardized B = 0.51; partial correlation = 0.542, r = 0.631) was found, as well as positive correlation of AHI with tonsillar size (standardized B = 0.246; partial correlation = 0.295,R = 0.489) in the multivariate forward stepwise regression analysis. ConclusionEven though we are aware that PSG is the gold standard for diagnostics of SDB there is a significant financial burden for this diagnostic procedure. That is why there is a necessity for establishing good clinical standards and possible formula for OSA severity evaluation. We propose formula which includes Mallampati score and tonsillar size for OSA -risk calculation in order to perform early therapeutic intervention thereby reducing the risk of long-term negative consequences. We recommend this formula as the screening formula in circumstances where PSG is not available, in cases when the “waiting list” is too long or when a child can not cooperate to perform it.In developing countries like Croatia on time intervention with reduced procedure–associated costs is of the utmost importance.

Preoperative Predictors of 30-Day Mortality and Prolonged Length of Stay after Above-Knee Amputation

The above-knee amputation (AKA) is an operation of last resort with high postoperative morbidity and mortality. This study identifies preoperative risk factors predictive of both 30-day mortality and extended length of stay (LOS) in AKA patients. Two hundred ninety-five AKA patients from 2004 to 2013 from a single institution were retrospectively reviewed using a deidentified electronic medical record. Rationally selected factors potentially influencing 30-day mortality and LOS were chosen, including demographics, etiologies, vascular surgical history, lifestyle factors, comorbidities, and laboratory values. Variables trending with one of the end points on bivariate analysis (P≤0.10) were entered into multivariate forward stepwise regression models to determine independence as a risk factor (P≤0.05). Subgroup analysis of AKA patients without a traumatic, burn, or malignant etiology was similarly conducted. Within the 295 patient cohort, 60% of the patients were male, 18% were African American, mean age was 58years and mean body mass index was 28kg/m(2). The 30-day mortality rate was 9%, and mean postoperative LOS of discharged patients was 9.3days. Upon logistic regression, thrombocytopenia (platelet count<250×10(6)/mL, P<0.001, odds ratio 6.1) and preoperative septic shock (P=0.02, odds ratio 5.1) were identified as independent risk factors for 30-day mortality. Upon linear regression, burn etiology (P<0.001, B=15.8days), leukocytosis (white blood cell count>12×10(6)/mL, P<0.001, B=6.2days), and guillotine amputation (P<0.001, B=7.6days) were independently associated with prolonged LOS. Excluding patients with AKAs due to trauma, burn, or malignancy, only thrombocytopenia (platelet count<250×10(6)/mL, P<0.001, odds ratio 10.2) and leukocytosis (white blood cell count>12×10(6)/mL, P=0.01, B=5.2days) were independent risk factors for in-hospital mortality and prolonged LOS, respectively. Preoperative septic shock and thrombocytopenia are independent risk factors for 30-day mortality after AKA, while burn etiology, leukocytosis, and guillotine amputation contribute to prolonged LOS. Awareness of these risk factors may help enhance both preoperative decision making and expectations of the hospital admission.

A novel non-invasive index using AFP and APTT is associated with liver fibrosis in patients with chronic hepatitis B infection: a retrospective cohort study

ObjectiveA liver biopsy is the ‘reference standard’ for diagnosing and staging liver fibrosis but with many disadvantages. Therefore, developing a non-invasive index for predicting fibrosis is very valuable. We developed...

Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma.

Background:Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC.Methods:Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann–Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied.Results:Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs.Conclusions:High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.

Timing and Perioperative Risk Factors for In-Hospital and Post-Discharge Venous Thromboembolism After Colorectal Cancer Resection

We postulated that the risk of venous thromboembolic disease (VTE) may persist after discharge and tested this hypothesis in patients undergoing colorectal resection for cancer. The American College of Surgeons National Surgery Quality Improvement Program database was queried for patients undergoing colorectal resections for cancer from 2005 to 2009. The outcome analyzed was a 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Multivariable forward stepwise regression was used to identify independent predictors of VTE. The database contained 21 943 colorectal cancer resections. The 30-day DVT rate was 1.4% (306 of 21 943), 29% (89 of 306) were diagnosed post-discharge. The 30-day PE rate was 0.8% (180 of 21 943), 33% (60 of 180) was diagnosed post-discharge, the combined DVT/PE rate was 2.0% (446 of 21 943). The median time to diagnosis of VTE was 9 days (interquartile range 4-16) after surgery. Post-discharge VTE rates in patients with length of stay (LOS) less than 1 week (0.6%) were similar to patients with LOS greater than 1 week (0.7%, Fisher exact P not significant). Independent risk factors for post-discharge VTE were preoperative steroid use for chronic condition (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.51-5.57, P = .001) and preoperative systemic inflammatory response syndrome (OR 2.26, 95% CI 1.24-4.10, P = .008). Diagnosis of almost one third of postoperative VTE in this patient population occurred after discharge. The duration of the prothrombotic stimulus of surgery is not well defined, and patients with malignancy are at high risk of VTE; thromboprophylaxis after discharge should be considered for these patients.

Association of blood transfusion and venous thromboembolism after colorectal cancer resection

IntroductionRed blood cell (RBC) transfusion is a common event in the perioperative course of patients undergoing surgery. Transfused blood can disrupt the balance of coagulation factors and modulates the inflammatory cascade. Since inflammation and coagulation are tightly coupled, we postulated that RBC transfusion may be associated with the development of venous thromboembolic phenomena. We queried the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) database to examine the relationship between intraoperative blood transfusion and development of venous thromboembolism (VTE) in patients undergoing colorectal resection for cancer. Materials and MethodsWe analyzed the data from 2005 to 2009 for patients undergoing colorectal resections for cancer based on the primary procedure CPT-4 code and operative ICD-9 diagnosis code. The primary outcome was 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Intraoperative transfusion of RBC's was categorized as: none, 1–2 units, 3–5 units and 6 units or more. DVT/PE occurrences were analyzed by multivariable forward stepwise regression (p for entry<.05, for exit>.10) to identify independent predictors of DVT. ResultsThe database contained 21943 colorectal cancer resections. The DVT rate was 1.4% (306/21943) and the PE rate was 0.8% (180/21943). Patients were diagnosed with both only 40 times and the combined DVT or PE rate (VTE) was 2.0% (446/21943). After adjusting for age, gender, race, ASA (American Society of Anesthesiologists) class, emergency procedure, operative duration and complexity of the procedure (based on Relative Value Units, RVU's), along with six clinical risk factors, intraoperative blood transfusion was a significant risk factor for the development of VTE and the risk increased with increasing number of units transfused. Preoperative hematocrit did not enter the multivariable model as an independent predictor of VTE, nor did open versus laparoscopic resection or wound class. ConclusionIn this study of 21943 patients undergoing colorectal resection for cancer, blood transfusion is associated with increased risk of VTE. Malignancy and surgery are known prothrombotic stimuli, the subset of patients receiving intraoperative RBC transfusion are even more at risk for VTE, emphasizing the need for sensible use of transfusions and rigorous thromboprophylaxis regimens.

Predictors of Exercise Capacity in Patients With and Without Type 2 Diabetes

PURPOSE: Exercise capacity is commonly impaired in persons with type 2 diabetes (T2DM), though the extent to which this relationship is influenced by the disease itself or related factors of age, gender, obesity, or left ventricular (LV) diastolic dysfunction is not entirely clear. Thus, we examined exercise capacity in persons with and without T2DM in relation to these demographic and physiological parameters. METHODS: Subjects (M=104, F=150), aged 30 to 65 yrs, were sedentary non-smokers without clinical heart disease. They were recruited for exercise and diet studies and were studied at baseline before the start of any intervention. 165 subjects (65%) had T2DM whereas 89 (35%) did not. Exercise capacity was expressed as VO2 peak during treadmill testing. Total percent body fat was measured by dual energy x-ray absorptiometry. LV diastolic function was assessed with 2-dimensional pulsed Doppler and tissue Doppler imaging echocardiography to yield peak E/A and peak E/E' ratios. RESULTS: Participants were 53.9 ± 8 years old and their BMI was 34.0 ± 4.5. VO2 peak was lower in females versus males, 21.3 ± 0.39 ml*kg*min-1 vs. 25.49 ± 0.48, p< 0.01, and in diabetics versus non-diabetics, 22.2 ± 5.4 vs. 24.4 ± 4.6 ml*kg*min-1, p<0.01. Using Pearson correlations, a higher VO2 peak was associated with younger age, r= -0.19, lower percent body fat, r= -0.44; higher peak E/A, r= 0.20; and lower E/E', r= -0.29; all p values were ≤ 0.001. Using multivariate forward stepwise regression, increased body fat and having diabetes were the strongest predictors of lower VO2 peak, each accounting for 16% of the observed variance. An additional 5% and 3% of the variance was explained by LV diastolic function (E/E') and age, respectively. All of these p values were ≤ 0.05. CONCLUSIONS: Reduced exercise capacity was most strongly related to higher levels of body fat and having diabetes with only modest contributions due to impaired LV diastolic function and older age. Given that reduced exercise capacity is a strong predictor of poor health outcomes and the growing prevalence of obesity and diabetes, these data suggest a compelling need for lifestyle and medical interventions to prevent or treat these conditions.

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

BackgroundVenous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.MethodsThis study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.ResultsThere were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.ConclusionsPravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.Trial RegistrationNot applicable when study undertaken.

Effects of Insulin Sensitivity, Body Composition, and Fitness on Lipoprotein Particle Sizes and Concentrations Determined by Nuclear Magnetic Resonance

Insulin resistance has been reported to be associated with development of atherogenic dyslipidemia. However, the confounding effects that obesity and low levels of cardiorespiratory fitness have on the relationship between insulin resistance and the development of atherogenic dyslipidemia remain to be adequately addressed. This study sought to examine the independent and combined effects of insulin sensitivity, body composition, and cardiorespiratory fitness on lipoprotein particle sizes and concentrations. Eight-four healthy, nondiabetic men (n = 43) and women (n = 41) were studied. The participants had a wide range of ages (18-30 and 65-80 yr), body composition (7.2-52.8% fat), and cardiorespiratory fitness (VO(2) peak, 13.5-66.2 ml/kg · min). Body composition, cardiorespiratory fitness, insulin sensitivity, and lipoprotein particle profiles were assessed using dual-energy x-ray absorptiometry, cardiopulmonary exercise testing, a hyperinsulinemic-euglycemic clamp, and nuclear magnetic resonance spectroscopy, respectively. Low levels of insulin sensitivity and cardiorespiratory fitness and higher levels of adiposity were associated with the accumulation of small, dense, low-density lipoprotein particles; small high-density lipoprotein particles; triglycerides; and very low-density lipoprotein particles. Multivariate forward-stepwise regression revealed that higher levels of adiposity, in particular truncal fat, were the strongest predictor of the lipoprotein particle size and concentration data, followed by insulin sensitivity. As expected, the accumulation of atherogenic lipoprotein particles (e.g. small, dense, low-density lipoprotein particles and small, high-density lipoprotein particles) was associated with low levels of insulin sensitivity, cardiorespiratory fitness, and higher levels of adiposity. However, multivariate forward-stepwise regression revealed that triglycerides, followed by truncal fat mass, were the strongest predictors of the lipoprotein particle size and concentration data.

Abstract Reasoning and Big Five Personality Correlates of Creativity in a British Occupational Sample

In the present study, 585 British adults attending an assessment center completed a series of tests that included measures of personality (the Revised NEO Personality Inventory), abstract reasoning (the Graduate and Managerial Assessment), and divergent thinking (DT; the Consequences Test). Correlation analyses showed that DT was significantly and positively correlated with abstract reasoning and the Big Five personality factors of Openness to Experience and Extraversion. A multivariate forward stepwise regression showed that DT was significantly predicted by “Openness,” Abstract Reasoning, Extraversion, and Agreeableness. Further analyses showed that DT was significantly correlated with 5 of the 6 Openness facets and 4 of the 6 Extraversion facets (as well as with several facets from Agreeableness, Neuroticism, and Conscientiousness). Overall, however, abstract reasoning and personality accounted for only 7% of the variance in DT, suggesting that these variables are only modestly associated wtih DT in a British occupational sample.

Impact of mediastinal, liver and lung 123I-metaiodobenzylguanidine (123I-MIBG) washout on calculated 123I-MIBG myocardial washout

PurposeIn planar 123I-metaiodobenzylguanidine (123I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating “washout” (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar 123I-MIBG images, with comparison to M as the best estimator of non-specific background activity.MethodsStudies on 98 subjects with both early (e) and late (l) planar 123I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]×100%.Results Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023).ConclusionAlthough increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar 123I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculations.

Variations in 123I-metaiodobenzylguanidine (MIBG) late heart mediastinal ratios in chronic heart failure: a need for standardisation and validation

BackgroundThere is lack of validation and standardisation of acquisition parameters for myocardial 123I-metaiodobenzylguanidine (MIBG). This lack of standardisation hampers large scale implementation of 123I-MIBG parameters in the evaluation of patients with chronic heart failure (CHF).MethodsIn a retrospective multi-centre study 123I-MIBG planar scintigrams obtained on 290 CHF patients (82% male; 58% dilated cardiomyopathy; New York Heart Association [NYHA classification] > I) were reanalysed to determine the late heart-to-mediastinum ratio (H/M).ResultsThere was a large variation in acquisition parameters. Multivariate forward stepwise regression showed that a significant proportion (31%, p < 0.001) of the variation in late H/M could be explained by a model containing patient-related variables and acquisition parameters. Left ventricular ejection fraction (p < 0.001), type of collimation (p < 0.001), acquisition duration (p = 0.001), NYHA class (p = 0.028) and age (p = 0.034) were independent predictors of late H/M.ConclusionsAcquisitions parameters are independent contributors to the variation of semi-quantitative measurements of cardiac 123I-MIBG uptake. Improved standardisation of cardiac 123I-MIBG imaging parameters would contribute to increased clinical applicability for this procedure.

Resistin in Preterm and Term Newborns: Relation to Anthropometry, Leptin, and Insulin

This study aimed to investigate 1) the plasma resistin concentration at birth, 2) the relationship of resistin with leptin and insulin, and 3) the association of resistin with anthropometric indexes in newborn infants. Blood samples for hormonal assay were obtained from preterm and term newborns within the first 2 h of life and before milk feeding or energy intake. Although these infants required blood sampling for clinical reasons, all were proved to be noninfected. Plasma resistin was significantly higher in term than in preterm infants. It was also significantly correlated with serum leptin, and both hormones were significantly associated with gestational age and anthropometric indexes. Infants who were born vaginally were found to have significantly higher plasma resistin levels compared with those who were born by cesarean section. In the multivariate forward stepwise regression models, resistin was found to be significantly associated with the mode of delivery and gestational age or birth weight. The association among resistin, leptin, and anthropometric indexes suggested that both hormones might be gestation related. A high circulating resistin level at term gestation could be advantageous to the infant by promoting hepatic glucose production and preventing hypoglycemia after birth. Infants who were born vaginally had significantly higher plasma resistin levels, suggesting that this hormone might also be associated with stress or inflammation induced by the birth process.