Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.

Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10-5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.

The Triangulation WIthin a STudy (TWIST) framework for causal inference within pharmacogenetic research.

In this paper we review the methodological underpinnings of the general pharmacogenetic approach for uncovering genetically-driven treatment effect heterogeneity. This typically utilises only individuals who are treated and relies on fairly strong baseline assumptions to estimate what we term the 'genetically moderated treatment effect' (GMTE). When these assumptions are seriously violated, we show that a robust but less efficient estimate of the GMTE that incorporates information on the population of untreated individuals can instead be used. In cases of partial violation, we clarify when Mendelian randomization and a modified confounder adjustment method can also yield consistent estimates for the GMTE. A decision framework is then described to decide when a particular estimation strategy is most appropriate and how specific estimators can be combined to further improve efficiency. Triangulation of evidence from different data sources, each with their inherent biases and limitations, is becoming a well established principle for strengthening causal analysis. We call our framework 'Triangulation WIthin a STudy' (TWIST)' in order to emphasise that an analysis in this spirit is also possible within a single data set, using causal estimates that are approximately uncorrelated, but reliant on different sets of assumptions. We illustrate these approaches by re-analysing primary-care-linked UK Biobank data relating to CYP2C19 genetic variants, Clopidogrel use and stroke risk, and data relating to APOE genetic variants, statin use and Coronary Artery Disease.

Comparative assessment of the clinical outcomes of clear aligners compared to fixed appliance in class II malocclusion.

OBJECTIVE: This study compared clinical outcomes between aligners and fixed appliances in class II adolescent patients. MATERIALS AND METHODS: Records of 31 aligners and 35 fixed class II patients, aged 13.5 ± 1.6 years were compared. Class II elastics was the mechanism employed for correcting the malocclusion. DI scores were used to compare initial complexity, and the PAR index scores were used to compare the clinical outcomes. Data on demographics, treatment and finishing durations, number of visits and refinements, duration of class II correction, and changes in the IMPA were collected. RESULTS: The mean pre-, post-treatment, and overall reduction in PAR index scores between the groups were not significantly different (P > 0.05). The clear aligners group had significantly shorter treatment duration (20.0 ± 11.6 months) than the fixed group (27.4 ± 9.1 months) (P < 0.001). The number of visits for the aligners' group was significantly less (12.7 ± 6.2) than in the fixed group (17.8 ± 5.8) (P < 0.001). Duration for class II correction was significantly shorter for clear aligners (13.3 ± 10.0 months) compared to the fixed group (17.4 ± 9.0 months) (P = 0.026). A smaller post-treatment change in IMPA (2 ± 6°) was detected in the aligners group compared to the fixed group (5 ± 6°) (P < 0.05). CONCLUSIONS: Treatment outcomes for aligners in class II adolescent patients were comparable to those achieved in fixed appliances. Shorter treatment and class II correction durations, fewer visits, and better control for the IMPA were noticed in the aligners' group. CLINICAL RELEVANCE: Treating class II adolescent patients with aligners seems promising and demands shorter treatment time and fewer visits.

Short- and long-term effects of conventional and miniscrew-assisted rapid palatal expansion on hard tissues using voxel-based superimposition of serial cone-beam computed tomography scans.

INTRODUCTION: The objective of this study was to evaluate the short-term and long-term hard-tissue changes with miniscrew-assisted rapid palatal expansion (MARPE) and rapid palatal expansion (RPE) compared with a matched control group with voxel-based superimposition using 3-dimensional cone-beam computed tomography (CBCT) scans. METHODS: A total of 180 CBCT scans were analyzed for 60 patients with a mean age of 13.9 years at 3 time points: pretreatment (T1), postexpansion (T2), and posttreatment (T3). Patients were divided into 3 groups: MARPE, RPE, and controls. Voxel-based superimposition was performed for CBCTs from T1 to T2 and T1 to T3 using the anterior cranial base as a reference. The hard-tissue surfaces were extracted after the superimposition procedure. Nine landmarks were analyzed: nasion, A-point, pogonion, left and right alar bases, zygoma, and gonion. Within-group changes were analyzed using linear mixed-effects models, including a random intercept per subject and the mixed effect of time (T1, T2, or T3) with test P values adjusted for multiple testing using Tukey's method. Between-group changes were analyzed using linear mixed-effects models, including a random intercept per subject and the mixed effects of time, group, and group × time interaction with P values adjusted for multiple testing using the Benjamin-Hochberg false discovery rate method. RESULTS: In the short term, both MARPE and RPE led to a significant downward movement of the right gonion and lateral movement of the right alar base compared with controls at T2 (P <0.05). In addition, MARPE led to a significant downward movement of pogonion and left gonion. RPE led to a significant downward movement of the A-point and lateral movement of the left alar base compared with controls at T2 (P <0.05). However, in the long-term, no changes were observed between the groups at T3. CONCLUSIONS: There were significant differences in pogonion, alar base, and gonion between MARPE, RPE, and control groups in the short term. However, all the hard-tissue changes were transient, as there were no differences between the 3 groups in the long term.

Calcium-channel blockers: Clinical outcome associations with reported pharmacogenetics variants in 32 000 patients.

AIMS: Pharmacogenetic variants impact dihydropyridine calcium-channel blockers (dCCBs; e.g., amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in pharmacogenomics knowledge base PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB. METHODS: We analysed up to 32 360 UK Biobank participants prescribed dCCB in primary care (from UK general practices, 1990-2017). We investigated 23 genetic variants. Outcomes were incident diagnosis of coronary heart disease, heart failure (HF), chronic kidney disease, oedema and switching antihypertensive medication. RESULTS: Participants were aged 40-79 years at first dCCB prescription. Carriers of rs877087 T allele in RYR3 had increased risk of hazard ratio (HF 1.13: 95% confidence interval 1.02 to 1.25, P = .02). Although nonsignificant after multiple testing correction, the association is consistent with prior evidence. We estimated that if rs877087 T allele could experience the same treatment effect as noncarriers, the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95% confidence interval 3.1 to 15.4). In patients with a history of heart disease prior to dCCB (n = 2296), rs877087 homozygotes had increased risk of new coronary heart disease or HF compared to CC variant. rs10898815 in NUMA1 and rs776746 in CYP3A5 increased likelihood of switching to an alternative antihypertensive. The remaining variants were not strongly or consistently associated with studied outcomes. CONCLUSION: Patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of pharmacogenetics variants supported by clinical evidence of association with adverse events.

Characterizing orthodontic tooth movement in real time using dental monitoring scans: A pilot study.

OBJECTIVES: This pilot study aimed to quantify the magnitude and type of tooth movement occurring in short time intervals within the regular monthly orthodontic visits for patients with fixed appliances and undergoing maxillary canine retraction. Additionally, this pilot study aimed to provide a descriptive evaluation for the accuracy and reliability of the Dental Monitoring (DM)-captured scans to those of an iTero digital scans in an extraction space closure model. SETTINGS AND SAMPLE POPULATION: 3D intraoral photographic scans (DM) for 12 patients with maxillary first premolar extractions in a single-centre academic institution. MATERIALS AND METHODS: Twelve patients treated with fixed appliances and undergoing space closure for maxillary premolar extraction(s) were included. Nickel-titanium (200 g) closing coil springs were used for canine retraction. At initiation of space closure (T1), iTero scans were acquired, and patients were instructed to take DM scans every 4-5 days until their next visit in 4-5 weeks (T2). At T2, a final iTero scan in addition to a DM scan was taken. The number of patients who did the scans regularly as instructed declined as time elapsed. Stereolithography (STL) files generated from the DM scans were superimposed with the STL files from the iTero scans using GOM Inspect software to determine the accuracy of the DM 3D models. To assess rate, type and direction of tooth movement, each of the 3D image STL files generated from the DM scans, taken every 4-5 days by each patient, was superimposed on the previously captured scan. The rate of tooth movement for the maxillary molars and canines was calculated in the 3 planes of space (X, Y, Z) at each time point, until the end of the experiment. RESULTS: Preliminary results indicated that the maxillary canines appeared to be displaced the greatest amount in the first 4-5 days with initial distolateral movement. As time elapsed, the rate of tooth movement decreased, and the tooth started moving distolingually. CONCLUSIONS: Dental monitoring software provides a high-tech platform to monitor tooth movement in a 'real-time' approach. Accuracy of the photographic scans in relationship to the intraoral scans appears promising. There seems to be some evidence that the greatest amount of movement occurs initially in the first few days after activation, dropping thereafter to become a slower constant rate of tooth movement.

Assessment of the occlusal outcomes in patients treated with orthognathic surgery and clear aligners.

OBJECTIVE: This retrospective two-centre study aimed to evaluate the occlusal outcomes in patients undergoing orthognathic surgery with clear aligners. METHODS: A retrospective chart review and occlusal outcomes for 15 patients (10 females and five males) with different types of dentofacial deformities in the anteroposterior, vertical and transverse dimensions, who underwent orthognathic surgery in conjunction with clear aligners were evaluated. Weighed Peer Assessment Rating (PAR) index scores of the pre-treatment and post-treatment digital models were used to assess initial complexity, final occlusal outcomes and degree of improvement with surgery and clear aligners. RESULTS: The mean post-treatment PAR score was 3.5 ± 2.54, which was a statistically significant improvement from the pre-treatment PAR score of 27.63 ± 12.09, an 87% improvement was achieved. All subcategories of the PAR index showed statistically significant improvement except for midline assessment component. CONCLUSIONS: Occlusal outcomes with aligners showed great improvement as indicated with the PAR index scores. Orthognathic surgical cases can be treated efficiently with aligners and future studies should compare occlusal outcomes between orthognathic surgical patients treated with clear aligners and those treated with fixed appliances.

Survival and failure rate of lower lingual bonded retainers: A retrospective cohort evaluation.

OBJECTIVE: The objectives of the study were to evaluate the survival rates for lower lingual retainers (LLRs) and to establish a correlation between patients' treatment-related factors (age, sex, malocclusion, appliance used for treatment, teeth bonded, retention protocols) to the survival of LLRs. MATERIALS AND METHODS: A total of 765 subjects [474 females and 291 males: mean age = 24.29 ± 10.67 years] between 2013 and 2022 were included. A customized data collection form was utilized to gather the data from the electronic health record (EHR) of subjects. Patient-related factors, crowding or spacing, deep bite or open bite and duration of treatment were extracted from patients' files. Kaplan-Meier estimator was used for the survival function, whereas Cox proportional hazards regression models were used to associate risk factors with retainer survival. RESULTS: 328 (42.9%) subjects had their LLRs failed, and the survival period was on average 17.37 ± 22.85 months. On the other hand, the follow-up period for the retainers that did not fail was on average 47.19 ± 23.66 months. 192 (28.3%) subjects had segment failure (retainer detached from 3 teeth or less), while 51 (7.5%) subjects had failures in more than 3 teeth (complete). None of the evaluated clinical variables were significantly associated with LLRs failure except for the bite category (P = .013) and the appliance used for treatment (P < .001). CONCLUSION: Success rate for LLRs was 57.1% over 47.19 months, failure rate was 42.9% over 17.37 months. The presence of deep bite and treatment with aligners were significantly associated with increased failure rate.

Dental implant and bone augmentation treatment in bone-compromised patients: Oral health-related quality of life outcomes.

STATEMENT OF PROBLEM: Patient-reported outcomes represent an additional and often overlooked measure of dental implant and bone augmentation treatment. Few implant studies have evaluated patient-reported outcomes in those with systemic bone compromise. PURPOSE: The purpose of this cohort study was to assess oral health-related quality of life (OHRQoL) outcomes in postmenopausal women receiving dental implants with normal bone density or mild osteopenia ("healthy" group; all DXA T-scores at femoral neck, total hip, and L1-L4 spine>-2.0) versus moderate osteopenia or osteoporosis ("bone compromised" group; any DXA T-score at femoral neck, total hip, or L1-L4 spine≤-2.0). MATERIAL AND METHODS: A total of 115 patients were recruited at the University of Connecticut School of Dental Medicine as part of a standard of care, prospective, nonrandomized cohort study. All participants received 1 of 3 bone augmentation procedures with implant placement. At baseline and at various intervals after implant placement, OHRQoL was measured by using the Oral Health Impact Profile-14 (OHIP-14) and surveys of patient expectations and satisfaction. These measures were compared between healthy and bone compromised groups (α=.05). RESULTS: For all OHRQoL measures across linear mixed effects models, no significant differences were found between bone groups at baseline and at each time point after implant placement (P>.05). Using the minimally important difference (MID) for OHIP-14, no definitive clinical differences were found in patient outcomes between bone groups at all postimplant time points (P>.05). From baseline to 24 months after implant placement, both healthy and bone compromised groups exhibited significant improvements in OHIP-14 and patient expectations scores (P<.05). While no within group differences were found in patient satisfaction scores, the mean satisfaction score remained high over time in both groups. CONCLUSIONS: Patient-reported outcomes as measured through OHIP-14, patient expectations, and patient satisfaction surveys suggest similar postimplant OHRQoL improvement in healthy and bone compromised individuals. OHRQoL improvements between bone groups were similar both in continuity and in scope, with no evidence of statistically significant score differences between groups at 24 months after implant placement across all measures and with no definitive evidence of clinical differences as measured by OHIP-14 MID comparisons across all timepoints.

Assessment of clear aligner accuracy of 2 clear aligners systems.

INTRODUCTION: This study compared treatment efficacy for specific tooth movements between 2 clear aligner systems (Clarity [3M Oral Care Solutions, St Paul, Minn] and Invisalign [Align Technology, San Jose, Calif]). METHODS: The study sample included 47 patients (7 males, 40 females; mean age, 36.57 ± 15.97 years) treated with Invisalign and 37 (4 males, 33 females; mean age, 34.30 ± 16.35 years) treated with Clarity aligners who completed their first set of aligners and had an initial refinement scan. Initial and predicted models were obtained from the initial simulated treatment plan. The first model of the refinement scan was labeled as achieved. SlicerCMF software (version 3.1; http://www.slicer.org) was used to superimpose the achieved and predicted digital models over the initial ones with regional superimposition on the relatively stable first molars. Nine hundred forty teeth in the Invisalign system were measured for horizontal, vertical, and angular movements and transverse width and compared with similar measurements of 740 teeth for the Clarity aligners. The deviation from the predicted was calculated and compared between both systems. RESULTS: The deviation achieved from the predicted was significant between the groups for the mandibular interpremolar and intercanine widths (P <0.05). Clarity aligners significantly undercorrected rotations compared with Invisalign for the mandibular first premolars, mandibular canines, maxillary canines, and maxillary central incisors. There was no statistically significant difference between the groups for the achieved vs predicted movements in the horizontal and vertical planes (P >0.05). CONCLUSIONS: The efficacy of clear aligner therapy systems (Clarity and Invisalign) in treating mild and moderate malocclusions was comparable. Deviation of the achieved movements from the predicted was greatest for rotational and vertical movements.

Comparison of electronic versus mechanical torque-limiting devices for dental implants: An in vitro study.

PURPOSE: To determine the accuracy of new electronic torque-limiting devices (ET) when compared to new and used conventional-style beam-type (BT) mechanical torque-limiting devices and hand-piece style (HS) mechanical torque-limiting devices. The secondary purpose was to compare any difference in accuracy between new and used mechanical torque-limiting devices, and any difference in accuracy when used on a straight versus an angled screw channel abutment. MATERIALS AND METHODS: A total of five torque-limiting devices were used to obtain 2000 readings under standardized conditions. An implant analog was fastened into a digital torque meter, to which an abutment was connected. Pre-determined torque values of 15 Ncm and 35 Ncm were applied, and actual torque values were recorded. A straight and an angled abutment were used to record 1000 readings each using the five torque-limiting devices. An overall Kruskal-Wallis test was applied to compare the median deviation among devices followed by a pairwise comparison ( = 0.05). RESULTS: For a target torque value of 15 Ncm on a straight abutment, the electronic device (ET) was statistically more accurate than the beam type (BT) new (p < 0.001) and used (p < 0.048) devices but less accurate than the hand-piece style (HS) used device (p < 0.001). On an angled abutment for a target value of 15 Ncm, the electronic device (ET) was statistically more accurate than hand-piece style (HS) new and used devices (p < 0.001). For a target torque value of 35 Ncm on a straight abutment, the ET was statistically more accurate than the HS new device (p < 0.001) but less accurate than the BT new device (p < 0.001). On an angled abutment for a target value of 35 Ncm, the electronic device (ET) was statistically less accurate than the beam-type (BT) new device (p < 0.001), the beam-type (BT) used device (p = 0.001), and the hand-piece style (HS) used device (p < 0.001). The electronic device (ET) was the only device accurate within the ISO standard of accuracy of 6% for each of the target torque value/abutment design combinations. There was no statistically significant difference related to the type of abutment used (angled vs. straight). CONCLUSIONS: Electronic torque limiting devices (ET) are an acceptable method for delivering torque for implant restorations for straight and angled abutments at 15 Ncm and 35 Ncm torque values. Conventional style beam-type (BT) mechanical torque-limiting devices are a simple, predictable, validated, and inexpensive tool for delivering accurate torque at 15 Ncm and 35 Ncm torque values. The hand-piece style (HS) mechanical torque-limiting devices are predictable to deliver 15 Ncm torque values.

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: Long-term outcomes in women and men.

OBJECTIVE: To estimate the effect of rs4149056 (SLCO1B1*5) genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. METHODS AND ANALYSIS: This study comprised 69 185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40-79 years at first prescription, treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5 mmol/L) at baseline, plus treatment discontinuation. RESULTS: A total of 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol vs 41.7% of those with functioning SLCO1B1 (odds ratio 1.31, 95% confidence interval [CI] 1.1-1.55, P = .001). Fewer males had high cholesterol and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (hazard ratio [HR] 1.19, 95% CI 1.03-1.37, P = .01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3, 95% CI 1.08-1.56, P = .006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. CONCLUSIONS: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve the effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.

Comparable Skeletal and Dental Movements Achieved Using Conventional and Surgery-First Techniques in Class III Patients.

PURPOSE: The surgery-first (SF) approach to orthognathic surgery has been proposed as a more efficient method to correct the dentofacial deformity. This study aimed to evaluate if the magnitude of skeletal and dental changes achieved in Class III patients treated with either conventional orthognathic surgery (COS) or SF techniques differ. METHODS: A retrospective cohort study of Class III orthognathic surgery patients between January 2006 and May 2020 with available pre- and post-treatment lateral cephalograms was conducted at an academic institution. The primary predictor variable was surgery technique: COS or SF. Assessed outcome variables included cephalometric skeletal parameters: SNA, SNB, ANB, Wits Appraisal, Sn-GoGn, and FMA; and dental parameters: U1-SN, U1-NA (°), U1-NA (mm), L1-NB (°), L1-NB (mm), and overjet. Within-group posttreatment parameters were analyzed with paired t tests. Pretreatment, posttreatment, and between-group parameter changes were analyzed by 2-sided 2-sample independent t tests. Potential covariates, including gender, surgical procedure, previous conventional treatment, extractions (excluding 3rd molars), crowding, and midline discrepancy, were analyzed using Fisher exact tests. RESULTS: Thirty-nine subjects were included in this study: 1) 21 COS (age: 20.9 ± 8.7 years) and 2) 18 SF (age: 19.6 ± 5.0 years). Cohorts were comparable (P > .05) for all analyzed covariates. COS showed statistically significant increases in L1-GoGn (3.31 ± 6.23°; P = .024), overjet (4.26 ± 3.99 mm; P < .001), ANB (3.5 ± 2.79°; P < .001), SNA (3.5 ± 1.85°; P < .001), and Wits Appraisal (3.78 ± 4.97 mm; P = .002). SF showed statistically significant increases in L1-GoGn (4.19 ± 4.85°; P = .002), L1-NB (3.08 ± 4.13°; P = .006), L1-NB (0.79 ± 1.35 mm; P = .023), overjet (5.82 ± 2.96 mm; P < .001), ANB (5.51 ± 3°; P < .001), SNA (4.13 ± 2.38°; P < .001), and Wits Appraisal (5.92 ± 3.42 mm; P < .001) and statistically significant decreases in U1-NA (-3.69 ± 7.35°; P = .048) and SNB (-1.38 ± 2.14°; P = .014). There were no statistically significant differences in skeletal or dental parameters between groups when adjusted for pretreatment levels of that parameter. The mean treatment duration was 38 months (standard deviation = 12.7) in COS and 17.6 months (standard deviation = 5.2) in SF. CONCLUSIONS: The results show that skeletal and dental changes between groups were not statistically different, despite an average 20-month difference in treatment duration. This suggests that either technique can be used to achieve comparable degrees of skeletal and dental movement in Class III patients.

Long-term effects of conventional and miniscrew-assisted rapid palatal expansion on root resorption.

INTRODUCTION: The purpose of this study was to use cone-beam computed tomography to compare immediate and long-term effects of conventional and miniscrew-assisted rapid palatal expansion (MARPE) appliances on root resorption in 2 treatment groups and a control group. METHODS: One hundred eighty cone-beam computed tomography images of 60 patients at 3 time points were assessed: initial, postexpansion, and debond. The patients were divided into 3 groups: control (n = 19), rapid palatal expansion (RPE) appliance (n = 21), and MARPE (n = 20). The period of initial to debond varied for the 3 groups: 2 years, 7 months for controls; 2 years, 9 months for RPE; and 2 years, 8 months for MARPE. The length of mesiobuccal, distobuccal, and palatal root of the maxillary first molar (1M); the buccal root of maxillary first premolar; and second premolar were measured. The inclination of the 1M, intercuspal width (ICW), interroot width (IRW), ICW/IRW ratio, maxillary skeletal width were measured in all 3 groups at different time points. RESULTS: Immediately after expansion, RPE and MARPE groups showed a significant increase in the molar inclination, ICW, ICW/IRW ratio, and maxillary skeletal width compared with controls at postexpansion. However, the long-term comparison did not show any significant difference for root resorption and expansion parameters between the 3 groups, except the ICW/IRW ratio, which was higher in MARPE than controls at debond. A significant negative association was observed between the length of the mesiobuccal root of 1M and molar inclination (ß = -0.025; 95% confidence interval, -0.050 to 0.0008; P <0.05). The expansion of ICW and IRW did not show a significant association with root resorption. CONCLUSIONS: The long-term outcomes showed no difference in the amount of root resorption between the RPE, MARPE, and control groups. Molar inclination showed a significant negative association with the length of the mesiobuccal root of the 1M.

Association between initial complexity, frequency of refinements, treatment duration, and outcome in Invisalign orthodontic treatment.

INTRODUCTION: This study explored possible associations between treatment duration, initial complexity, outcomes in Invisalign therapy, and the number of refinements. METHODS: Three-dimensional models (initial, final, and refinements) of 355 Invisalign patients (114 males and 241 females; 33.8 ± 17.1 years) were analyzed using the Peer Assessment Rating (PAR) index questionnaire tool in the Ortho Analyzer software (version 2.0; 3Shape, Copenhagen, Denmark) to calculate the weighted total and individual PAR index scores for each component of the PAR index. Data related to demographics, treatment duration, and the number of refinements were collected. RESULTS: Treatment duration increased as the number of refinements increased. Percent of improvement was higher in PAR ≥22 group than PAR <22 with an increase in the number of refinements: 83.3% vs 73.8% for 2 refinements; 94.7% vs 91.2% for 3 refinements; and 100% vs 85.7% for ≥4 refinements. Those who achieved great improvement or improvement and those who did not were significantly different in treatment duration (P <0.001 and P = 0.027), number of refinements (≥3 refinements; P <0.001), initial occlusal severity (PAR ≥22; P <0.01 and P = 0.031). Most subjects achieved improvement after the first refinement (64.5% for PAR <22 and 78.5% for PAR ≥22). Few had ≥4 refinements, and if they did, none achieved improvement with additional refinements. CONCLUSIONS: Initial complexity for an Invisalign case is associated with treatment duration, achieved outcomes, and the number of refinements. Treatment duration increased with an increased number of refinements. Great improvement or improvement for the first time dropped to 0 if additional refinements were carried out after 3. Therefore, performing additional refinements does not necessarily mean better occlusal outcomes.

Examining the Development of Operative Autonomy in Vascular Surgery Training and When Trainees and Program Directors Agree and Disagree.

BACKGROUND: Lack of autonomy in the operating room (OR) during general surgery residency is a major contributing factor to low confidence operating independently after graduation. Although attempts to address decreased autonomy and development of entrustment in the OR are being made in general surgery programs, this issue has not been examined thoroughly in vascular surgery. We sought to determine barriers and opportunities for developing operative autonomy during vascular surgery training by surveying program directors (PDs) and trainees (integrated residents and fellows) in U.S. vascular surgery training programs. METHODS: An anonymous electronic survey was sent via email to all PDs (n = 155) and trainees (n = 516) in United States vascular surgery training programs. Demographics, academic characteristics, and responses regarding factors impacting the development of entrustment were collected. RESULTS: Thirty-five PDs and 100 trainees completed the survey (22.5% and 19.4% response rate, respectively). Sixty percent of trainees were integrated residents and 40% were fellows. Twenty percent of PDs and 33% of trainees were female, and 5% of all PDs and trainees were from underrepresented minorities. The single most positive factor affecting the development of autonomy according to trainees and PDs is familiarity of the faculty with the trainee. Both PDs and trainees thought the trainee's preparation for the case positively affected development of autonomy; however, more PDs believed that involvement with preoperative preparation in particular (marking the patient, consenting the patient, filling out a history and physical, prepping and draping the patient) was important (P < 0.05). PDs believed that duty-hour limitations negatively affected the trainee's ability to develop autonomy in the OR, whereas more trainees believed that hospital or OR efficiency policies played a negative role (P < 0.05). Finally, compared with trainees, PDs believed that the appropriate amount of time for safe struggle before the attending should take over the case was when OR efficiency was compromised or at any moment the trainee is unsure of themselves (P < 0.05); trainees believed that the attending should take over the case after the limit of their skill set or troubleshooting ability was reached (P < 0.05). CONCLUSIONS: Familiarity of the attending physician with the trainee is an important positive factor for development of entrustment and autonomy in vascular surgery trainees. Duty-hour limitations and belief of the need for hospital efficiency may negatively impact operative independence of trainees. An open discussion about balancing OR efficiency and trainees' safe struggle is essential to address the growth of independent operative skills in vascular surgery trainees.

Esophageal dysmotility and lung disease in patients with systemic sclerosis: is there a possible association or correlation? A retrospective chart review.

OBJECTIVE: Our aim was to evaluate the relationship between esophageal dysmotility and lung disease by correlating the results of Echocardiogram and Pulmonary Function Test (PFT) with Esophageal Transit Study (ETT). METHODS: Charts of Systemic Sclerosis (SSc) patients fulfilling 2013 ACR/EULAR classification criteria seen in Rheumatology clinics were reviewed and their demographics, ETT result, PFT, and echocardiogram data were collected at baseline, years 1, 3, 5, and 10. Patients were divided based on their ETT status and were compared with respect to each variable using a two-sided two-sample t test for continuous variables and a Fisher's exact test for categorical variables. RESULTS: 130 patients were identified with either limited cutaneous SSc (109) or diffuse cutaneous SSc (21) with a mean age of 52.65 years. The mean DLCO was statistically worse in abnormal ETT patients [p value = 0.0004] as were the progression rates per year for DLCO at - 2.25 (p value = 0.019). Progression rate of FVC per year was statistically significant in the abnormal ETT group, although the mean value was not. The number of patients with abnormal PASP was not statistically different between the two groups (p values 0.104, 0.178, 0.653 at baseline, years 3 and 5, respectively). CONCLUSION: The presence of esophageal dysmotility was associated with increased pulmonary involvement in the form of abnormal DLCO with worsening progression rates per year. There was no statistically significant difference in PASP and FVC between the two groups; however, the progression rate for FVC was worse in adjusted models.

Biodegradable Piezoelectric Force Sensor.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Comparison of external apical root resorption with clear aligners and pre-adjusted edgewise appliances in non-extraction cases: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate and compare the amount of external apical root resorption (EARR) observed during the orthodontic treatment with pre-adjusted edgewise appliance (PEA) or clear aligner therapy (CAT) and with 2D or 3D radiographic methods of measuring the root resorption. SEARCH STRATEGY AND SELECTION CRITERIA: A search of PubMed MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, LILACS, Web of Science, Dissertations & Theses Global, ClinicalTrials.gov registry, and the ISRCTN Registry was performed. Studies that have evaluated the amount of root resorption in non-extraction cases using CAT or PEA were selected for the systematic review. A meta-analysis was performed for the amount of root resorption of permanent maxillary incisors using PEA or CAT treatment modalities by either 2D or cone-beam computed tomography radiographic examination. DATA COLLECTION AND ANALYSIS: Database research, elimination of duplicate studies, data extraction, and risk of bias were performed by authors independently and in duplication. A random-effect meta-analysis followed by subgroup comparisons were performed to evaluate EARR. RESULTS: A total of 16 studies (4 were prospective and 12 were retrospective) were identified for inclusion in the systematic review. The mean root resorption for the permanent maxillary incisors was in the range from 0.25 to 1.13 mm (overall: 0.49 mm; 95% confidence interval [CI] = 0.24 to 0.75 mm). The mean root resorption difference between CAT and PEA was statistically significant (P < 0.05) for 12 but not for 21, 11, or 22. LIMITATIONS: One of the drawbacks is a lack of good quality prospective studies, specifically randomized clinical trials in the literature. CONCLUSIONS AND IMPLICATIONS: Neither PEA or CAT technique leads to clinically significant root resorption (1 mm) of the maxillary incisors. The amount of EARR of maxillary incisors is not significant in comparing two treatment modalities (PEA and CAT), except for 12, where the PEA group has significantly more EARR when compared to CAT. REGISTRATION: The protocol for this systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 and was registered at PROSPERO database (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018113051). This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

The Influence of Age and Facial Expression (Eye Open/Closed) On Maxillary Dental and Gingival Display.

PURPOSE: To assess if there are any differences in maxillary dentogingival exposure between different facial expressions (maximum smile with eyes open and eyes closed), age groups and both sexes. MATERIAL AND METHODS: Digital photographs of the lower third of the face of 120 subjects, belonging to 6 different age groups were taken. There were 20 subjects in each of the 6 age groups (20-30, 30-40, 40-50, 50-60, 60-70, and 70-80) which were comprised of 80 women and 40 men. Two standardized images of each subject were taken, one of maximum smile with eyes open, and the second of maximum smile with eyes closed. These 240 images were used to quantify a dentogingival exposure ratio (DER) for each tooth spanning the second bicuspids on either side, using standardized measurement techniques. Additionally, incidence of interdental papilla visibility was studied in a binary manner, and all data were studied with respect to various covariables of age, sex and type of facial expression using a generalized linear mixed effects model. A p-value < 0.05 was determined to be statistically significant. RESULTS: There was a statistically significant difference between the dentogingival exposure ratio (DER) for all images with eyes open and eyes closed per tooth location studied, across all age groups (p ≤ 0.001) and both sexes, suggesting that subject images of smiles with eyes closed had significantly higher dentogingival exposure. There was a decreasing trend of DER with increasing age groups when eyes were open (p = 0.005) and when eyes were closed (p = 0.042), suggesting that older subjects had lower dentogingival exposure. With respect to sex, there was no statistically significant difference in mean DER between males and females, when eyes were open (p = 0.430) and closed (p = 0.351). The incidence of interdental papilla exposure also differed significantly between images with eyes open and eyes closed across all age groups (p ≤ 0.001). However, the incidence of interdental papilla exposure decreased with age, only in images with eyes open (p < 0.001) but was not statistically significant among images with eyes closed (p = 0.127). With respect to sex, there was a significant difference in incidence of interdental papilla exposure in images with eyes open (p = 0.029) but no significant difference when eyes were closed (p = 0.782). CONCLUSIONS: Maxillary dentogingival exposure decreases with increasing age and is significantly higher when recording maximum smile with eyes closed, for all age groups and both sexes. As this is a simple and clinically reproducible facial expression, incorporating patient's maximum smiling images with eyes closed may be routinely necessary for complete and accurate data collection for prosthodontic treatment planning purposes.