Genetic risk for major depressive disorder and loneliness in sex-specific associations with coronary artery disease.

Major depressive disorder (MDD) and loneliness are phenotypically and genetically correlated with coronary artery disease (CAD), but whether these associations are explained by pleiotropic genetic variants or shared comorbidities is unclear. To tease apart these scenarios, we first assessed the medical morbidity pattern associated with genetic risk factors for MDD and loneliness by conducting a phenome-wide association study in 18,385 European-ancestry individuals in the Vanderbilt University Medical Center biobank, BioVU. Polygenic scores for MDD and loneliness were developed for each person using previously published meta-GWAS summary statistics, and were tested for association with 882 clinical diagnoses ascertained via billing codes in electronic health records. We discovered strong associations with heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 controls. We found odds ratios of 1.11 (95% CI, 1.04-1.18; P 8.43 × 10-4) and 1.13 (95% CI, 1.07-1.20; P 4.51 × 10-6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Results were similar in patients without psychiatric symptoms, and the increased risk persisted in females even after adjusting for multiple conventional risk factors and a polygenic score for CAD. In a final sensitivity analysis, we statistically adjusted for the genetic correlation between MDD and loneliness and re-computed polygenic scores. The polygenic score unique to loneliness remained associated with CAD (OR 1.09, 95% CI 1.03-1.15; P 0.002), while the polygenic score unique to MDD did not (OR 1.00, 95% CI 0.95-1.06; P 0.97). Our replication sample was the Atherosclerosis Risk in Communities (ARIC) cohort of 7197 European-ancestry participants (1598 incident CAD cases). In ARIC, polygenic scores for MDD and loneliness were associated with hazard ratios of 1.07 (95% CI, 0.99-1.14; P = 0.07) and 1.07 (1.01-1.15; P = 0.03), respectively, and we replicated findings from the BioVU sensitivity analyses. We conclude that genetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in females.

Can the idealized voider derived flow indexes be a measure of voiding efficiency and how accurate are they?

OBJECTIVE: Our hypothesis was to confirm whether an idealized voider flow equation (IVFE) that we created is more accurate than trying to rely on estimated flow rates in the same patient in two consecutive voids. We also looked to confirm whether flow index (FI) can be a proxy for voiding efficiency and to identify which FI was best; those based off our own IVFE equations or those derived from the commonly used power equations. STUDY DESIGN: We used data from a previous study and calculated flow rates using our IVFE and the power equations. Descriptive statistics and non-parametric tests were performed along with error analysis using Bland Altman (BA) and accuracy analysis (AA). RESULTS: Bland Altman (BA) analysis revealed that flows obtained from normal voiders voiding between 100 and 200 cc as well as from 50 cc to 115% of EBC are comparable and tend to be reproducible in subsequent voids. FI derived from the IVFE exhibit less bias than Qmax making it a better way to compare these voids. A comparison of Qmax and flow index for different combinations of volumes and PVR's was done utilizing BA and accuracy measures both indicating that FI was more reproducible. CONCLUSION: The data support both of our hypothesis that flow index is a good measure of voiding efficiency. We have also shown that IVFE is a better and more accurate measure of calculating a flow index than the power equations regardless of the volume and PVR scenarios that are presented.

Are seasonal and income variations accountable for bowel and bladder dysfunction symptoms in children?

AIMS: Certain illnesses tend to occur more commonly at certain times of the year. It is also known that individuals of different socioeconomic groups have a predilection for physical ailments that in some cases may be related to poor access to healthcare or may be related to environmental or work related causes. We hypothesized that there may be a difference between patients from season to season and from different socioeconomic groups and their presenting lower urinary tract symptoms (LUTS). METHODS: We reviewed our electronic medical record going back for 5 years, selecting out all patients who presented to all 10 of our offices in a wide geographic area that covers 22 million people of all races and income levels in the Tristate area of New York. RESULTS: We identified 13,346 patients, 6,010 males and 6,957 females, and 379 were excluded for not meeting age inclusion criteria. The descriptive statistics based on age, median income for both males and females can be found in Tables I, II, III, and IV, respectively. Of note, males were older than females at presentation (8.1 vs. 6.9 years) with no difference in median incomes between families. There were more UTIs in females and more dysuria complaints in males. Urinary incontinence also appeared to be more prevalent in females than males, while males had more issues with fecal soiling than the females. What was obvious was that urgency and frequency was positively correlated with high income groups. On the other hand urinary incontinence represented either by itself or combined with UUI was more prevalent in the high school group. Fecal soiling was also more prevalent in the high school group. UTIs were more prevalent in the high school group but surprisingly there was no difference in patients that were not able to empty their bladders. Conversely we found that constipation was more prevalent in the professional group than in the other groups which is the opposite of the FS findings. Lastly dysuria appeared to be more prevalent in the P group. CONCLUSIONS: It is clear that there are marked differences in the results between high school income and professional income groups in particular with the U and F, along with C which correlate with high income professionals' children. UUI, UI, UTI, along with FS are associated with high school income parents. Neurourol. Urodynam. 36:148-154, 2017. © 2015 Wiley Periodicals, Inc.

Can a quantitative means be used to predict flow patterns: Agreement between visual inspection vs. flow index derived flow patterns.

INTRODUCTION: Uroflowmetry is a first-line tool in the evaluation of children with lower urinary tract symptoms. Unfortunately, there is a tremendous amount of intra- and interobserver variation in defining the shape of curves. Regrettably, one observer can see one flow as a tower and the other can call it a bell. Here lies the major flaw with the interpretation of uroflow shapes. Previously, we have shown that there is a good correlation between the calculated flow index (FI) and the shape of a flow curve (bell, tower and plateau) in normal children. OBJECTIVE: Our hypothesis was to show that the FI-defined shapes were as good or better than the present system of grading flow curves. If so this would help remove subjectivity from the field of uroflow assessment and make studies objective and easily compared. STUDY DESIGN: Consecutive uroflows of children who were being evaluated for lower urinary tract symptoms from two centers were reviewed and compared alongside those of presumed normal voiders; the shape of the curves were read by the same experienced readers at each institution. Only curves that were read as bell, plateau, and tower were compared with the curve patterns derived from the quantitative methods derived by one of the authors. FI was derived by taking the actual Qmax/estimated Qmax. RESULTS: There were 591 males and 1039 females who had uroflow studies, of these 409 and 819, respectively were read as either bell, towers, or plateaus The highest kappa value for males was 0.71 (CI 0.64-0.79) using a 3 × 3 matrix indicating substantial agreement. In females the highest kappa was 0.52 (CI 0.46-0.59) in the group 2 patients using the receiver operating characteristic cutoffs but the 1 SD cutoff was close with a kappa value of 0.51, which indicates moderate agreement (Table). DISCUSSION: Using the FI method we saw that there was substantial to moderate agreement using a quantitative method to define flow shapes based on the kappa values that were obtained in this study. The one fundamental flaw with shape determination in both visual and FI-derived methods is that the cutoffs are arbitrary since the visual defined shapes are the basis for the FI shapes. CONCLUSION: Our findings clearly showed that a FI-derived method of defining shapes is as accurate as visual inspection or more depending on the study. The greatest disagreement occurs in those grey or transition zones between plateau, bell and tower. This system could be useful in removing much of the ambiguity and difficulty in reading flows.

Can a simple question predict prolonged uroflow lag times in children?

OBJECTIVE: It is our experience that some children with bowel and bladder dysfunction (BBD) who have bladder neck dysfunction had a tendency to complain of dizziness when we subjected the patients with dizziness to tilt-table testing to confirm the diagnosis of autonomic dysfunction. From these findings we postulated that patients who complain of dizziness are likely to have prolonged lag times that are a proxy for bladder neck dysfunction (BND). STUDY DESIGN: This was an Institute Review Board-approved study in which we enrolled new patients in a sequential fashion who were referred to our outpatient urology offices for evaluation of BBD over a 3-month period. All patients were asked if they frequently experienced dizziness when they rapidly stood from a sitting or lying down position or when they raised their head rapidly. An analysis of the following parameters was undertaken: prevalence of dizziness, bladder neck dysfunction, and comorbid psychiatric problems. Uroflowmetry findings were analyzed as well. RESULTS: Tilt-table group: In the tilt-table group the median age of the patients was 14.5 (4.5-18) years for the five males and five females who were tested. All males and four out of five females experienced a blood pressure drops of 20 mmHg or more on table tilting and three experienced syncope. All patients had prolonged lag times, with an average lag time of 16.5 s. All these patients were able to tolerate alpha-blockers once they were adequately hydrated and salt loaded. Alpha-blocker dosing was increased gradually. In the questionnaire group, 212 patients were initially enrolled: 125 girls and 87 boys. Eleven of 12 males and eleven of 16 females had prolonged lag times when dizziness was present. Sensitivity was 92% and 69%, specificity was 80% and 91% respectively for male and females. Analysis of the psychiatric history revealed a statistically significant association with dizziness and neuropsychiatric problems in the patients and family members. CONCLUSION: We have been able to show a high degree of sensitivity in male patients and a high degree of specificity in female patients that a simple question, "Do you get dizzy on rising in the morning or with rapid standing?", is a reliable marker for BND in children. We have also seen that there is an association between dizziness and psychiatric problems in patients and in family members. It appears from our results and the available literature that autonomic dysfunction is commonly associated with BND and dizziness can be a simple proxy question to identify this problem.

A quantitative approach to the interpretation of uroflowmetry in children.

PURPOSE: We hypothesized that by correcting for volume and creating a flow index (FI) we could develop a reproducible and reliable means to estimate flows in children without the use of a flow nomogram. Our second hypothesis was that this volume corrected FI could define objective parameters for the different flow curves that are described in the ICCS document. METHODS: Uroflowmetry curves of 1,268 healthy children were analyzed. Quadratic equations using nonlinear regression for both sexes were generated for each set of presumed normal voiders (learning data) (NV). The NV test data were used to verify the equations. Linear regression analysis was used to compare the variance between actual and estimated flow rates. A FI (Actual Qavg/Estimated Qavg) was created and ROC analysis for all flow types was performed. Sensitivity and specificity analysis was performed on all voids to validate the accuracy of the FI to predict flow pattern. RESULTS: Analysis of the FI from the first void to the second confirmed the accuracy and reproducibility in both males and females using various means of analysis. ROC analysis shows that there are very strong AUC's for Bell, plateau, and tower flow patterns. Sensitivity and specificity analysis reveals that defined FI parameters are able to predict the flow patterns. CONCLUSION: Our predictive formulas allow for direct comparison of one flow to the next in a single patient when the FI is used. Utilizing the FI, we can predict the type of flow pattern removing subjectivity from the analysis of uroflow patterns. Neurourol. Urodynam. 35:836-846, 2016. © 2015 Wiley Periodicals, Inc.

Improving the accuracy of wide resection of bone tumors and enhancing implant fit: A cadaveric study.

BACKGROUND/AIMS: Customized three-dimensional (3-D) jigs have been shown to increase the accuracy of skeletal tumor resection in comparison to freehand techniques. However, the utility of these jigs in subsequently enhancing the fit of endoprosthetic implants has yet to be determined. We hypothesized that custom jigs would improve implant fit compared to freehand resection. METHODS: Nine matched pairs of cadaveric femurs were scanned by CT. The images then had 'virtual' tumors positioned on the distal medial femoral condyle and preoperative resection plans were generated. Custom implants were designed to fit into the resected spaces and 3-D printed. Similarly, customized 3-D jigs were designed and printed for half of the femurs. Resections were then performed using the jigs or freehand. The implants were positioned in the resected femurs and the accuracy-of-fit was quantitatively assessed by re-scanning the resected femurs and calculating the deviation from the implant (in degrees) for each of the 3 cutting planes. The results were then compared between jig and freehand resections. RESULTS: For the first plane, the jig resulted in less deviation than the freehand cut, but it did not achieve statistical significance. However, for the 2nd and 3rd planes, the jigs deviated 1.78° and 2.20° from the implants compared to 4.41° and 7.96° for the freehand cuts, both of which were statistically significant improvements (p = 0.038 and p = 0.003). CONCLUSION: In summary, customized 3-D jigs were shown to improve the accuracy-of-fit between implants and host bone, moving this technology closer to clinical implementation.