The Management of Large Bladder Calculi by Utilizing Dual-Action Percutaneous Lithotripsy via Suprapubic Tube Sheath: A Novel Technique.

Bladder calculi commonly develop in patients with poor bladder emptying or those with retained foreign bodies within the bladder, leading to irritative voiding symptoms, hematuria, and an increased likelihood of refractory urinary tract infections. While many techniques exist for the treatment of bladder calculi, including endoscopic and open-surgical approaches, our novel technique may help manage exceptionally large or difficult-to-treat bladder calculi effectively. We present three patients with symptomatic bladder calculi ranging from 1.3 cm to 6.8 cm in size who were successfully treated by using our novel technique. Percutaneous access to the bladder was obtained by using a suprapubic catheter trocar and sheath to enable the utilization of a dual-action lithotriptor. Sheath insertion and lithotripsy were performed under direct visualization with a rigid cystoscope via the native urethra. This technique is easily learned and can be safely employed in patients in whom other methods may pose risks of higher morbidity.

Pediatric pneumomediastinum: Symptom-based management.

BACKGROUND: Pediatric spontaneous pneumomediastinum is known to have a benign course. Despite this, there is no consensus or standardization for the workup and management. There are often a variety of imaging studies performed for patients with similar presentations. METHODS: This is a retrospective chart review evaluating the presentation, workup, and management of all pediatric patients with a primary diagnosis of spontaneous pneumomediastinum over a 5-year period at a children's hospital. RESULTS: Of the 62 patients, the initial workup consisted of either a chest x-ray (CXR) only (n = 31, 50%), a chest computed tomography scan only (n = 11, 18%) or both (n = 14, 23%); additionally, some patients came with 'other' imaging only (n = 3, 5%) or no imaging (n = 3, 5%). Twenty-seven patients (44%) underwent an additional CXR and 19 (31%) underwent an esophagram. All esophagrams were negative for an esophageal leak. A presenting symptom of pain was associated with a hospital stay of less than 24 h (p = 0.008) while shortness of breath (p = 0.0005) and emesis (p = 0.0006) were associated with a hospital stay of greater than 24 h. Associated diagnoses of respiratory infections (p = 0.02) and gastrointestinal issues (p = 0.006), such as hyperemesis, were associated with inpatient admission. CONCLUSION: Pediatric patients with spontaneous pneumomediastinum benefit from evaluation, management, and treatment based on their presenting symptoms. There is an opportunity to decrease unnecessary radiation exposure in this patient population with fewer CXRs and avoidance of esophagrams, neither of which alter management. LEVEL OF EVIDENCE: Level III.

Differential effects of chronotype on physical activity and cognitive performance in older adults.

Introduction: Chronotypes reflect individuals' preferred activity and sleep patterns (e.g., "morning-types" vs. "evening-types") and are associated with health and physical activity. Less is known about the relationship between chronotype and cognitive health in older adults. It is unclear whether chronotype's influence is driven by sleep timing or disruption. This study explored the relationship between chronotype, physical activity, and cognitive performance in older adults with and without self-reported sleep disorders. Methods: Participants were 153 older adults (M = 70.35, SD = 5.89) who wore an Actigraph on the non-dominant wrist for seven days to measure total physical activity, peak physical activity, and chronotype (sleep interval midpoint). We categorized participants as morning-, evening-, and intermediate-chronotypes and assessed cognitive performance in domains of attention, executive function, and verbal memory. Results: MANCOVAs showed patterns of activity across the 24-hour day differed between chronotypes such that morning-types were active earlier and evening-types active later, ps > .001. Total physical activity and average peak activity did not differ between chronotypes, (ps ≥ .117). Timing of peak activity followed expectations (morning-types peaked earliest (p = .019). Evening-types exhibited significantly worse executive function and attention than intermediate-types, p = .008. When excluding participants with sleep disorders, evening-types engaged in significantly less total physical activity than other groups, but cognitive performance did not differ. Discussion: We found no differences in total or peak physical activity between groups, which is inconsistent with findings from studies in younger samples. This suggests the role of chronotype on physical activity may change with age and points to the potential impact of methodological discrepancies. While evening-types exhibited worse executive function and attention performance, this finding disappeared when participants with sleep disorders were excluded. Sleep dysregulation rather than sleep timing may be driving this difference. Recent trends in physical activity research explore activity patterns across the 24-hour day and acknowledge codependence between different activity types. Our findings suggest chronotype and activity timing may be important as researchers advance this line of research in older adults.

Physical Activity and the Acute Hemodynamic Response to ACE Inhibition in Hypertension.

Introduction. Physical activity (PA) can reduce blood pressure (BP) in hypertensives through possibly interacting with the renin-angiotensin-aldosterone system (RAAS). We conducted a nested-cohort analysis to determine if self-reported PA was associated with BP responsiveness to acute angiotensin converting enzyme inhibition (ACEi). Methods. Data were extracted from the HyperPATH dataset, a cohort designed to identify mechanisms of cardiometabolic risk. Hypertensives that completed a self-assessed PA questionnaire, hormonal assessments (aldosterone [ALDO]), and BP to a single dose of an ACEi (captopril, 25 mg) were included. All participants (n = 144) were studied on a controlled diet for 7 days. PA was recorded as no PA, or little, moderate, or high amounts of exercise. Analyses were adjusted for age, sex, race, and body mass index. Results. Individuals who reported high amounts of PA displayed a greater BP lowering effect from ACEi compared to those who reported moderate (-14.8 ± 8.1 vs -8.4 ± 9.9 mm Hg, P < .01) or no additional PA (-14.8 ± 8.1 vs -2.6 ± 9.9 mm Hg, P < .001). Exploratory analyses indicated high amounts of PA were associated with a reduced heart rate (54 ± 8 vs 66 ± 10 bpm, P < .001) and blunted ALDO (ß = 0.44, 95% confidence interval = 0.19-0.70). Conclusions. Higher self-reported PA was associated with an augmented BP lowering effect to acute ACEi in hypertensive patients.

Effect of adrenocorticotropic hormone infusion on circulating sclerostin levels.

Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/ß-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/ß-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids' adverse effects on bone. The aim of this study was to determine whether an acute infusion of cosyntropin (i.e. ACTH(1-24)), which increases endogenous cortisol, increases serum sclerostin levels as compared to a placebo infusion. This study was performed using blood samples obtained from a previously published, double-blind, placebo-controlled, randomized, cross-over study among healthy men and women who received infusions of placebo or cosyntropin after being supine and fasted overnight (ClinicalTrials.gov NCT02339506). A total of 17 participants were analyzed. There was a strong correlation (R2 = 0.65, P < 0.0001) between the two baseline sclerostin measurements measured at the start of each visit, and men had a significantly higher average baseline sclerostin compared to women. As anticipated, cosyntropin significantly increased serum cortisol levels, whereas cortisol levels fell during placebo infusion, consistent with the diurnal variation in cortisol. There was no significant effect of cosyntropin as compared to placebo infusions on serum sclerostin over 6-24 h (P = 0.10). In conclusion, this randomized, placebo-controlled study was unable to detect a significant effect of a cosyntropin infusion on serum sclerostin levels in healthy men and women.

CONSENSUS: a Shiny application of dementia evaluation and reporting for the KU ADC longitudinal Clinical Cohort database.

BACKGROUND: The University of Kansas Alzheimer's Disease Center (KU ADC) maintains several large databases to track participant recruitment, enrollment, and capture various research-related activities. It is challenging to manage and coordinate all the research-related activities. One of the crucial activities involves generating a consensus diagnosis and communicating with participants and their primary care providers. PROCESS: To effectively manage the cohort, the KU ADC utilizes a combination of open-source electronic data capture (EDC) (i.e. REDCap), along with other homegrown data management and analytic systems developed using R-studio and Shiny. PROCESS EVALUATION: In this article, we describe the method and utility of the user-friendly dashboard that was developed for the rapid reporting of dementia evaluations which allows clinical researchers to summarize recruitment metrics, automatically generate letters to both participants and healthcare providers, which ultimately help optimize workflows. CONCLUSIONS: We believe this general framework would be beneficial to any institution that build reports and summarizing key metrics of their research from longitudinal databases.

A clinical trial to evaluate the effect of statin use on lowering aldosterone levels.

BACKGROUND: Statins are the first-line pharmaceutical agent in the management of hypercholesterolemia and cardiovascular (CV) risk reduction, and the most commonly prescribed class of drugs worldwide. Studies describing CV risk reduction independent of LDL-cholesterol lowering have evoked an interest in the pleiotropic mechanisms of statins' benefits. We recently demonstrated that administration of statins in animal models lowers aldosterone levels and observed an association between statin use and reduced aldosterone levels in two human cohorts, with lipophilic statins displaying a greater effect than hydrophilic statins. Therefore, we designed a randomized, placebo-controlled, double-blinded intervention study to assess whether statin treatment lowers aldosterone in a type-dependent manner in humans, with simvastatin (lipophilic) showing a greater effect than pravastatin (hydrophilic). METHODS/DESIGN: One hundred five healthy participants will be recruited from the general population to enroll in a 12-week, randomized, placebo-controlled, double-blinded, 3-arm clinical trial. Ninety participants are anticipated to complete the protocol. After baseline assessment of aldosterone levels, participants will be randomized to daily simvastatin, pravastatin, or placebo. Aldosterone levels will be assessed after 2 days on study drug and again after 6 weeks and 12 weeks on study drug. Prior to each aldosterone assessment, participants will consume an isocaloric sodium and potassium-controlled run-in diet for 5 days. Assessments will occur on an inpatient research unit to control for diurnal, fasting, and posture conditions. The primary outcome will compare 12-week angiotensin II-stimulated serum aldosterone by study drug. Secondary outcomes will compare baseline and 12-week 24-h urine aldosterone by study drug. DISCUSSION: Results from this rigorous study design should provide strong support that statins lower aldosterone levels in humans. These results may explain some of the beneficial effects of statins that are not attributed to the LDL-lowering effect of this important class of medications. Results would demonstrate that statin lipophilicity is an important attribute in lowering aldosterone levels. The outcomes of this program will have implications for the design of studies involving statin medications, as well as for the differential use of classes of statins. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02871687 ; First Posted August 18, 2016.

Attitudes toward advance care planning among persons with dementia and their caregivers.

OBJECTIVES: To examine factors that influence decision-making, preferences, and plans related to advance care planning (ACP) and end-of-life care among persons with dementia and their caregivers, and examine how these may differ by race. DESIGN: Cross-sectional survey. SETTING: 13 geographically dispersed Alzheimer's Disease Centers across the United States. PARTICIPANTS: 431 racially diverse caregivers of persons with dementia. MEASUREMENTS: Survey on "Care Planning for Individuals with Dementia." RESULTS: The respondents were knowledgeable about dementia and hospice care, indicated the person with dementia would want comfort care at the end stage of illness, and reported high levels of both legal ACP (e.g., living will; 87%) and informal ACP discussions (79%) for the person with dementia. However, notable racial differences were present. Relative to white persons with dementia, African American persons with dementia were reported to have a lower preference for comfort care (81% vs. 58%) and lower rates of completion of legal ACP (89% vs. 73%). Racial differences in ACP and care preferences were also reflected in geographic differences. Additionally, African American study partners had a lower level of knowledge about dementia and reported a greater influence of religious/spiritual beliefs on the desired types of medical treatments. Notably, all respondents indicated that more information about the stages of dementia and end-of-life health care options would be helpful. CONCLUSIONS: Educational programs may be useful in reducing racial differences in attitudes towards ACP. These programs could focus on the clinical course of dementia and issues related to end-of-life care, including the importance of ACP.

A semi-automated pipeline for fulfillment of resource requests from a longitudinal Alzheimer's disease registry.

OBJECTIVE: Managing registries with continual data collection poses challenges, such as following reproducible research protocols and guaranteeing data accessibility. The University of Kansas (KU) Alzheimer's Disease Center (ADC) maintains one such registry: Curated Clinical Cohort Phenotypes and Observations (C3PO). We created an automated and reproducible process by which investigators have access to C3PO data. MATERIALS AND METHODS: Data was input into Research Electronic Data Capture. Monthly, data part of the Uniform Data Set (UDS), that is data also collected at other ADCs, was uploaded to the National Alzheimer's Coordinating Center (NACC). Quarterly, NACC cleaned, curated, and returned the UDS to the KU Data Management and Statistics (DMS) Core, where it was stored in C3PO with other quarterly curated site-specific data. Investigators seeking to utilize C3PO submitted a research proposal and requested variables via the publicly accessible and searchable data dictionary. The DMS Core used this variable list and an automated SAS program to create a subset of C3PO. RESULTS: C3PO contained 1913 variables stored in 15 datasets. From 2017 to 2018, 38 data requests were completed for several KU departments and other research institutions. Completing data requests became more efficient; C3PO subsets were produced in under 10 seconds. DISCUSSION: The data management strategy outlined above facilitated reproducible research practices, which is fundamental to the future of research as it allows replication and verification to occur. CONCLUSION: We created a transparent, automated, and efficient process of extracting subsets of data from a registry where data was changing daily.

The Relationship Between Apolipoprotein ε4 Carrier Status and Sleep Characteristics in Cognitively Normal Older Adults.

The apolipoprotein (APOE) ε4 allele, a well-described genetic risk factor for late-onset Alzheimer disease (AD), is associated with sleep disturbances even in cognitively normal older adults, although it is not clear whether this association is independent of sleep apnea. We sought to extend previous studies by examining whether cognitively normal older adults without self-reported sleep apnea who carry the APOE ε4 allele have altered sleep characteristics compared to noncarriers. Data from N = 36 (APOE ε4 carriers [n = 9], noncarriers [n = 27]) cognitively normal older adults (Clinical Dementia Rating [CDR] scale = 0) without self-reported sleep apnea were used for these analyses. Participants wore an actigraph for 7 days to determine sleep characteristics. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to assess sleep quality and daytime sleepiness, respectively. The APOE ε4 carriers had a higher number of awakenings compared to the noncarriers ( P = .02). There was no significant difference in the PSQI global score and the ESS; however, the PSQI subcomponent of daily disturbances was significantly higher in APOE ε4 carriers ( P = .03), indicating increased daytime dysfunction is related to disrupted sleep. This study provides evidence that individuals who are cognitively normal and genetically at risk of AD may have disrupted sleep. These findings are consistent with prior studies and suggest that sleep disruption may be present in the presymptomatic stages of AD.