Yunro Chung

Patients with primary membranous nephropathy are at high risk of cardiovascular events

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

Dosimetric distribution to tooth-bearing areas in intensity-modulated radiation therapy for head and neck cancer: a pilot study

OBJECTIVES Dosimetric distribution of intensity-modulated radiotherapy (IMRT) to tooth-bearing areas for common head and neck (H&N) cancer sites were analyzed to facilitate minimization of osteoradionecrosis (ORN) risk through preradiation dental treatment planning. STUDY DESIGN Fifty-four patients received IMRT with prescribed doses ranging from 6000 centigrays (cGy) (adjuvant) to 6930 cGy (primary) to treat base of tongue (BOT), tonsil, larynx, nasopharynx, and hypopharynx cancers. The average maximal radiation dose delivered was recorded in tooth-bearing areas (anteriors, premolars, and first, second, and third molars) of the maxilla and mandible. RESULTS All tooth-bearing areas in laryngeal cancer cases received less than 2500 cGy. Maxillary and mandibular molar regions for BOT, tonsil, and hypopharynx cancers received 5000 cGy or higher. In nasopharynx cancers, maxillary teeth received higher doses than mandibular teeth. CONCLUSIONS Among 5 H&N subsites, mandibular molar regions for BOT, tonsil, and hypopharynx cancers received higher IMRT doses on average, posing the greatest ORN risk.

A Predictive Model for Root Caries Incidence

This study aimed to find the set of risk indicators best able to predict root caries (RC) incidence in caries-active adults utilizing data from the Xylitol for Adult Caries Trial (X-ACT). Five logistic regression models were compared with respect to their predictive performance for incident RC using data from placebo-control participants with exposed root surfaces at baseline and from two study centers with ancillary data collection (n = 155). Prediction performance was assessed from baseline variables and after including ancillary variables [smoking, diet, use of removable partial dentures (RPD), toothbrush use, income, education, and dental insurance]. A sensitivity analysis added treatment to the models for both the control and treatment participants (n = 301) to predict RC for the control participants. Forty-nine percent of the control participants had incident RC. The model including the number of follow-up years at risk, the number of root surfaces at risk, RC index, gender, race, age, and smoking resulted in the best prediction performance, having the highest AUC and lowest Brier score. The sensitivity analysis supported the primary analysis and gave slightly better performance summary measures. The set of risk indicators best able to predict RC incidence included an increased number of root surfaces at risk and increased RC index at baseline, followed by white race and nonsmoking, which were strong nonsignificant predictors. Gender, age, and increased number of follow-up years at risk, while included in the model, were also not statistically significant. The inclusion of health, diet, RPD use, toothbrush use, income, education, and dental insurance variables did not improve the prediction performance.

Six-year clinical performance of etch-and-rinse and self-etch adhesives

OBJECTIVE To evaluate the 6-year clinical performance of Xeno IV, Xeno III, and XP Bond adhesives in the restoration of non-carious cervical lesions (NCCLs). METHODS This was a randomized controlled clinical trial where 39 participants met the inclusion/exclusion criteria and were enrolled. Lesions restored were notch-shaped NCCLs. Prior to adhesive procedures, NCCLs were roughened. No enamel bevel was placed and no mechanical retention was created. Adhesive systems were applied following manufacturers instructions and the NCCLs were restored with composite resin (TPH(3)). Restorations were finished immediately after placement and scored with regard to retention, marginal discoloration, marginal adaptation, sensitivity, and secondary caries using modified USPHS criteria. Descriptive statistics were performed. Logistic regression models were performed for each outcome separately with compound symmetry correlation structure where teeth were clustered by participants. All analyses were conducted using SAS 9.2. RESULTS The 6-year recall rate was 77.5% of the restorations (76.9% of the participants). No statistical differences were found between adhesives for retention, marginal discoloration, and marginal adaptation. Restorations failed by loss of retention (16.7%, 27.6%, and 11.8% of Xeno IV, Xeno III, and XP Bond restorations, respectively) and marginal discoloration (7.4% of Xeno IV restorations). For every unit increase in restoration volume it was 1.31 (95%C.I. 1.05, 1.63, P=0.01) times more likely that the restoration retention would be maintained. SIGNIFICANCE The tested adhesive systems presented similar clinical performance after six years of service, with annual failure rates of 2.8%, 4.6%, and 2.0% for Xeno IV, Xeno III, and XP Bond, respectively.

Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients

Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 μM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 μM/min given by intermittent schedules. DLTs at doses over 8000 μM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.).

One-Year Water Sorption and Solubility of All-in-One Adhesives

The aim of this study was to evaluate the water sorption and solubility of different adhesives. Adper Easy Bond, Adper Single Bond Plus, Bond Force, Clearfil SE Bond (bonding resin only), and Xeno IV were the materials evaluated. Ten disks of each adhesive were made in Teflon molds and evaporation of any volatile components was allowed. The disks were weighed daily in an analytical balance until a constant mass was obtained (m1). Disks were then immersed in water for 12 months when their wet weight was recorded (m2). The disks were again weighed daily until a constant mass was obtained and the final weight recorded (m3). Water sorption and solubility (percentages) were calculated using the recorded mass values. Kruskal-Wallis tests were used to compare the average water sorption and solubility among the different adhesives. Mann-Whitney tests with a Bonferroni correction were used to determine the pairwise differences between adhesives in water sorption and solubility. The level of significance was set at 0.05. Water sorption and solubility were significantly different among the groups (p<0.05). Pairwise comparisons showed no significant differences (p>0.05) between Adper Single Bond Plus and Bond Force, or between Clearfil SE Bond and Xeno IV in either water sorption or solubility. Xeno IV did not differ from Adper Easy Bond in water sorption (p>0.05). Water sorption and solubility of all-in-one adhesives increased with time, and the rates of increase were composition-dependent. The results suggest that monomers other than HEMA contribute to water sorption and solubility of adhesive systems from different categories.

Evaluation of a Test Dose Strategy for Pharmacokinetically Guided Busulfan Dosing for Hematopoietic Stem Cell Transplantation

Targeted busulfan dosing helps limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplantation (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy using a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (>9 mg/kg) conditioning between January 2014 and October 2015. A weight-based test dose of 0.8 mg/kg was used with PK assessments to predict area under the curve (AUCpred) achieved with weight-based dosing, with a target AUC of 4800 µM*minute (AUCtarget). PK from the test dose was then used to calculate a PK-guided first myeloablative busulfan dose. PK assessments were also done after the first dose to assess if the goal area under the curve (AUC) had been achieved (AUCfirst). A PK-guided first dose resulted in achievement of target AUC with target ranges of ±10% in 50% of patients, ±15% in 75%, and ±20% in 94%. This was an improved rate of target achievement compared with the 33%, 44%, and 63% of patients who achieved the desired AUC for these respective target ranges when using weight-based dosing (P = .12, .004, and <.001, respectively). The PK-guided strategy also decreased the variability of AUC from 3.6-fold in AUCpred from the weight-based test doses (2700.8 to 9631 µM*minute; SD, 1211.6 µM*minute) to 1.8-fold in AUCfirst from the PK-guided first doses (3672.1 to 6609.8 µM*minute; SD, 574.7 µM*minute). This reflects a 2-fold improvement in AUC variability with a PK-guided dosing strategy. This is also improved from the 3-fold variability in AUC reported in other studies. Weight and body surface area were significantly associated with the likelihood of AUCfirst being within the ±10% target range (P = .04 for both associations). There was no significant association between AUCfirst and death, relapse, or a composite of the two. These results demonstrate a significant improvement in target AUC attainment and less interpatient variability with PK-guided dosing using a test dose strategy compared with weight-based dosing.

Complementary and alternative medicine use among children with mental health issues: results from the National Health Interview Survey

BackgroundMental health issues in children have become a serious public health concern in the U.S. within the past few decades. Emerging evidence suggests that Complementary and Alternative Medicine (CAM) can be beneficial for various mental health issues. However, little is known about the prevalence, reasons, and associated factors of CAM use among this population in the U.S. The purpose of this study is to examine the characteristics of CAM use among U.S. children with mental health issues.MethodsUtilizing the 2012 National Health Interview Survey data, we used descriptive analysis, Wald F-statistics, and multivariable survey logistic regression models to examine the prevalence, patterns, and associated factors of CAM use in children aged 4–17 (n = 10,233) adjusting for the complex sampling design.ResultsCAM use is more popular among children with mental health issues compared with those without (19.2% vs. 10.1%, p < 0.001). Herbal remedies (9.1%), mind-body therapies (5.5%), and chiropractic care (5.3%) were the most frequently used modalities. Primary reasons for children to use CAM are because they are helpful (69.2%), natural (55.9%), and holistic (44.7%). The majority of CAM users perceived CAM therapies are helpful. Predictors of CAM use are children who are female, whose parents had a higher educational level and socioeconomic status, and who had at least one co-morbid medical condition. Only 18.4% of CAM usage was recommended by medical doctors.ConclusionsApproximately 10 million parents of children with mental health issues reported the use of CAM therapies, mainly because of their desire for a more natural and holistic healthcare approach. Given that the majority of CAM users perceived CAM therapies as helpful, future studies should investigate the unique contributions of CAM in pediatric psychiatric care. Because a low percentage of CAM use was recommended by medical doctors, educational interventions designed to equip medical professionals with CAM knowledge and experience will be conducive to improving effective patient-physician communication in clinical settings. Since CAM use is reported as more prevalent by parents’ of children with higher education and family income, effective strategies designed to reduce disparities in accessing promising CAM therapies are warranted.

The Yngve Ericsson Prize: Progress in Prophylactic Dentistry Research Awarded

imal intervention dentistry concept. His latest line of research has resulted in the development of a novel carious lesion assessment and treatment instrument (CAST) for use in epidemiological studies. Dr. Frencken’s solid and highly dedicated research has contributed greatly to the prevention of dental diseases and to increasing the accessibility of oral health care for many individuals and population groups in different countries worldwide. Panos Papapanou is Professor of Dental Medicine, Director of the Division of Periodontics, and Chairman of The 2016 Yngve Ericsson Prize for Research in Preventive Odontology has been awarded jointly to Professor Jo Frencken of Radboud University, Nijmegen, the Netherlands, and Professor Panos Papapanou of Columbia University, New York, NY, USA. The Prize of SEK 400,000 (approx. EUR 43,000) is to be shared equally between the two recipients and will be awarded at the ORCA Congress in July in Athens, Greece. Jo Frencken, Associate Professor Emeritus in Minimal Intervention Dentistry at the College of Dental Sciences of the Radboud University Medical Centre in Nijmegen, is a public health specialist by training. His early experience, in Malawi, Africa, of the many facets of oral health in the absence of regular dental care significantly altered his perception on how dental caries might be managed, and this led him to reconsider how oral care can be made available for an increasing number of people and communities. Dr. Frencken’s research has thus mainly focused on caries prevention and on providing dental care by principles that were earlier deemed less justifiable but currently considered as valid, given the fact that low-income populations cannot afford the well-known standards of oral care. He pioneered the development of the ART (atraumatic restorative treatment) concept and was instrumental in researching the many aspects of this minPublished online: June 4, 2016

Effects of Lip Revision Surgery on Long-Term Orosensory Function in Patients with Cleft Lip/Palate

Objective To determine whether secondary lip revision surgery impacts sensitivity of the upper lip. Design A three-group, parallel, prospective, nonrandomized clinical trial. Setting University of North Carolina School of Dentistry. Patients, Participants Three groups: (1) patients with repaired cleft lip/palate who were scheduled for lip revision (revision; N = 20); (2) patients with repaired cleft lip/palate who did not receive a lip revision (non-revision; N = 13); and (3) non-cleft control subjects (non-cleft; N = 22). Interventions Lip revision surgery. Main Outcome Measures Measures of (1) two-point perception threshold (two-point), (2) warmth detection threshold (warm), and (3) cool detection threshold (cool) were obtained from two sites on the upper lip vermilion. The revision participants were tested approximately 1 week before surgery and then approximately 3 and 12 months after surgery. The non-revision and non-cleft participants were tested at similar times. Results There were no significant differences among the three groups at baseline for two-point, warm, or cool. The main effects of group, age, sex, and time were not statistically significant for the two-point or warm (p > .05). The mean differences between the 3- and 12-month follow-up visits and baseline for two-point and warm were small for all three groups. For cool, group was statistically significant (p = .04), the difference in the non-revision group between follow-up and baseline was 31% to 34% higher than in the non-cleft group (p = .01). Conclusions Although at postsurgery revision participants exhibited threshold values comparable to presurgical values, the sensory differences observed among subgroups of participants with cleft lip are complex.