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Item Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials(American Heart Association, 2023) Fletcher, Robert A.; Arnott, Clare; Rockenschaub, Patrick; Schutte, Aletta E.; Carpenter, Lewis; Vaduganathan, Muthiah; Agarwal, Rajiv; Bakris, George; Chang, Tara I.; Heerspink, Hiddo J. L.; Jardine, Meg J.; Mahaffey, Kenneth W.; Neal, Bruce; Pollock, Carol; Jun, Min; Rodgers, Anthony; Perkovic, Vlado; Neuen, Brendon L.; Medicine, School of MedicineBackground: Sodium glucose cotransporter‐2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results: Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions: In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect.Item Clinical Outcomes of 0.018-Inch and 0.022-Inch Bracket Slot Using the ABO Objective Grading System(E.H Angle Education and Research Foundation, 2010-05-01) Detterline, David A.; Isikbay, Serkis C.; Brizendine, Edward J.; Kula, Katherine S.; Orthodontics and Oral Facial Genetics, School of DentistryObjective: To determine if there is a significant difference in the clinical outcomes of cases treated with 0.018-inch brackets vs 0.022-inch brackets according to the American Board of Orthodontics (ABO) Objective Grading System (OGS). Materials and Methods: Treatment time and the ABO-OGS standards in alignment/rotations, marginal ridges, buccolingual inclination, overjet, occlusal relationships, occlusal contacts, interproximal contacts, and root angulations were used to compare clinical outcomes between a series of 828 consecutively completed orthodontic cases (2005–2008) treated in a university graduate orthodontic clinic with 0.018-inch- and 0.022-inch-slot brackets. Results: A two-sample t-test showed a significantly shorter treatment time and lower ABO-OGS score in four categories (alignment/rotations, marginal ridges, overjet, and root angulations), as well as lower total ABO-OGS total score, with the 0.018-inch brackets. The ANCOVA—adjusting for covariants of discrepancy index, age, gender, and treatment time—showed that the 0.018-inch brackets scored significantly lower than the 0.022-inch brackets in both the alignment/rotations category and total ABO-OGS score. Conclusions: There were statistically, but not clinically, significant differences in treatment times and in total ABO-OGS scores in favor of 0.018-inch brackets as compared with the 0.022-inch brackets in a university graduate orthodontic clinic (2005–2008).Item Does Nonsurgical Periodontal Treatment Improve Systemic Health?(Sage, 2021) Taylor, H.L.; Rahurkar, S.; Treat, T.J.; Thyvalikakath, T.P.; Schleyer, T.K.; Health Policy and Management, School of Public HealthClinicians frequently stress the importance of maintaining good oral health for multiple reasons, including its link to systemic health. Because periodontal treatment reduces inflammation in oral tissues, some hypothesize it may positively affect systemic outcomes by reducing inflammation in the body. A significant number of systematic reviews (SRs) and meta-analyses (MAs) have evaluated the effect of periodontal treatment on systemic outcomes. However, inconsistent findings and questionable methodological rigor make drawing conclusions difficult. We conducted a systematic review of reviews that studied the effect of nonsurgical periodontal treatment on systemic disease outcomes. We report on outcomes evaluated, categorizing them as biomarkers, and surrogate or clinical endpoints. In addition, we used A MeaSurement Tool to Access systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality of the reviews. Of the 52 studies included in our review, 21 focused on diabetes, 15 on adverse birth outcomes, 8 on cardiovascular disease, 3 each on obesity and rheumatoid arthritis, and 2 on chronic kidney disease. Across all studies, surrogate endpoints predominated as outcomes, followed by biomarkers and, rarely, actual disease endpoints. Ninety-two percent of studies had "low" or "critically low" AMSTAR 2 confidence ratings. Criteria not met most frequently included advance registration of the protocol, justification for excluding individual studies, risk of bias from individual studies being included in the review, and appropriateness of meta-analytical methods. There is a dearth of robust evidence on whether nonsurgical periodontal treatment improves systemic disease outcomes. Future reviews should adhere more closely to methodological guidelines for conducting and reporting SRs/MAs than has been the case to date. Beyond improved reviews, additional rigorous research on whether periodontal treatment affects systemic health is needed. We highlight the potential of large-scale databases containing matched medical and dental record data to inform and complement future clinical research studying the effect of periodontal treatment on systemic outcomes.Item Hybrid Diffusion Imaging in Mild Traumatic Brain Injury(Mary Ann Liebert, 2018-10-15) Wu, Yu-Chien; Mustafi, Sourajit M.; Harezlak, Jaroslaw; Kodiweera, Chandana; Flashman, Laura A.; McAllister, Thomas W.; Radiology and Imaging Sciences, School of MedicineMild traumatic brain injury (mTBI) is an important public health problem. Although conventional medical imaging techniques can detect moderate-to-severe injuries, they are relatively insensitive to mTBI. In this study, we used hybrid diffusion imaging (HYDI) to detect white matter alterations in 19 patients with mTBI and 23 other trauma control patients. Within 15 days (standard deviation = 10) of brain injury, all subjects underwent magnetic resonance HYDI and were assessed with a battery of neuropsychological tests of sustained attention, memory, and executive function. Tract-based spatial statistics (TBSS) was used for voxel-wise statistical analyses within the white matter skeleton to study between-group differences in diffusion metrics, within-group correlations between diffusion metrics and clinical outcomes, and between-group interaction effects. The advanced diffusion imaging techniques, including neurite orientation dispersion and density imaging (NODDI) and q-space analyses, appeared to be more sensitive then classic diffusion tensor imaging. Only NODDI-derived intra-axonal volume fraction (Vic) demonstrated significant group differences (i.e., 5-9% lower in the injured brain). Within the mTBI group, Vic and a q-space measure, P0, correlated with 6 of 10 neuropsychological tests, including measures of attention, memory, and executive function. In addition, the direction of correlations differed significantly between groups (R2 > 0.71 and pinteration < 0.03). Specifically, in the control group, higher Vic and P0 were associated with better performances on clinical assessments, whereas in the mTBI group, higher Vic and P0 were associated with worse performances with correlation coefficients >0.83. In summary, the NODDI-derived axonal density index and q-space measure for tissue restriction demonstrated superior sensitivity to white matter changes shortly after mTBI. These techniques hold promise as a neuroimaging biomarker for mTBI.Item Multi-Center Study of Outcomes Among Persons with HIV who Presented to US Emergency Departments with suspected SARS-CoV-2(Wolters Kluwer, 2021-08-31) Bennett, Christopher L.; Ogele, Emmanuel; Pettit, Nicholas R.; Bischof, Jason J.; Meng, Tong; Govindarajan, Prasanthi; Camargo, Carlos A., Jr.; Nordenholz, Kristen; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground: There is a need to characterize patients with HIV with suspected severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2). Setting: Multicenter registry of patients from 116 emergency departments in 27 US states. Methods: Planned secondary analysis of patients with suspected SARS-CoV-2, with (n=415) and without (n=25,306) HIV. Descriptive statistics were used to compare patient information and clinical characteristics by SARS-CoV-2 and HIV status. Unadjusted and multivariable models were used to explore factors associated with death, intubation, and hospital length of stay. Kaplan-Meier curves were used to estimate survival by SARS-CoV-2 and HIV infection status. Results: Patients with both SARS-CoV-2 and HIV and patients with SARS-CoV-2 but without HIV had similar admission rates (62.7% versus 58.6%, p=0.24), hospitalization characteristics (e.g. rates of admission to the intensive care unit from the ED [5.0% versus 6.3%, p=0.45] and intubation [10% versus 13.3%, p=0.17]), and rates of death (13.9% versus 15.1%, p=0.65). They also had a similar cumulative risk of death (log-rank p=0.72). However, patients with both HIV and SARS-CoV-2 infections compared to patients with HIV but without SAR-CoV-2 had worsened outcomes, including increased mortality (13.9% versus 5.1%, p<0.01, log rank p<0.0001) and their deaths occurred sooner (median 11.5 days versus 34 days, p<0.01). Conclusion: Among ED patients with HIV, clinical outcomes associated with SARS-CoV-2 infection are not worse when compared to patients without HIV, but SARS-CoV-2 infection increased risk of death in patients with HIV.Item The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications(MDPI, 2019-11-13) Aurilio, Gaetano; Piva, Francesco; Santoni, Matteo; Cimadamore, Alessia; Sorgentoni, Giulia; Lopez-Beltran, Antonio; Cheng, Liang; Battelli, Nicola; Nolè, Franco; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineObesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC–obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords “obesity”, “body mass index”, “overweight”, “renal cell carcinoma/kidney cancer”, “medical treatment”, “targeted therapy”, and “immunotherapy/immune checkpoint inhibitors”. The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.