Effect of analysis software program on measured deviations in complete arch, implant-supported framework scans.

STATEMENT OF PROBLEM: Implementation of fabrication trueness analysis by using a recently introduced nonmetrology-grade freeware program may help clinicians and dental laboratory technicians in their routine practice. However, knowledge of the performance of this freeware program when compared with the International Organization for Standardization recommended metrology-grade analysis software program is limited. PURPOSE: The purpose of this in vitro study was to evaluate the effect of an analysis software program on measured deviations in the complete arch, implant-supported framework scans. MATERIAL AND METHODS: A total of 20 complete arch, implant-supported frameworks were fabricated from a master standard tessellation language (STL) file from either polyetheretherketone (PEEK) or titanium (Ti) (n=10). All frameworks were then digitized by using different scanners to generate test STLs. All STL files were imported into a nonmetrology-grade freeware program (Medit Link) and a metrology-grade software program (Geomagic Control X) to measure the overall and marginal deviations of frameworks from the master STL file by using the root mean square (RMS) method. Data were analyzed by using the two 1-sided paired t test procedure, in which 50 µm was considered as the minimal clinically meaningful difference (α=.05). RESULTS: When overall RMS values were considered, the nonmetrology-grade freeware program was not inferior to the metrology-grade software program (P<.05). When marginal RMS values were considered, the nonmetrology-grade freeware program was inferior to the metrology-grade software program only when PEEK frameworks were scanned with an E4 laboratory scanner (P>.05). CONCLUSIONS: The use of the tested nonmetrology-grade freeware program resulted in overall deviation measurements similar to those when a metrology-grade software program was used. The freeware program was inferior when marginal deviations were analyzed on E4 scans of a PEEK framework, which was the only scanner-material pair that led to a significant difference, among the 15 pairs tested.

Patient-centered dosing: oncologists' perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC).

PURPOSE: Although metastatic breast cancer (MBC) is treatable, it is not curable and most patients remain on treatment indefinitely. While oncologists commonly prescribe the recommended starting dose (RSD) from the FDA-approved label, patient tolerance may differ from that seen in clinical trials. We report on a survey of medical oncologists' perspectives about treatment-related toxicity and willingness to discuss flexible dosing with patients. METHODS: We disseminated a confidential survey via social media/email in Spring 2021. Eligible respondents needed to be US-based medical oncologists with experience treating patients with MBC. RESULTS: Of 131 responses, 119 were eligible. Physicians estimated that 47% of their patients reported distressing treatment-related side effects; of these, 15% visited the Emergency Room/hospital and 37% missed treatment. 74% (n = 87) of doctors reported improvement of patient symptoms after dose reduction. 87% (n = 104) indicated that they had ever, if appropriate, initiated treatment at lower doses. Most (85%, n = 101) respondents did not believe that the RSD is always more effective than a lower dose and 97% (n = 115) were willing to discuss individualized dosing with patients. CONCLUSION: Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial and/or subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists.

Comparison of clinical outcomes between Invisalign and conventional fixed appliance therapies in adult patients with severe deep overbite treated with nonextraction.

INTRODUCTION: The use of aligner therapy for orthodontic treatment has increased substantially in the past decade. However, no study has compared treatment outcomes between the conventional fixed appliance and Invisalign therapies in patients with a severe deep overbite. METHODS: This study included 50 consecutive adult patients who underwent treatment with either Invisalign (n = 25; mean age, 23.3 ± 8.5 years) or a conventional fixed appliance (n = 25; mean age, 23.1 ± 6.5 years) to correct overbite >5 mm and >60% deep overbite. Cephalometric analysis and peer assessment rating was used to compare the clinical outcome between groups. RESULTS: Cephalometric analysis showed significant differences in N-Me (P = 0.0005) and Mp-L6 (P = 0.0001) between Invisalign and fixed appliance treatment groups. No significant differences were observed in the peer assessment rating analysis or total treatment duration between the 2 groups. CONCLUSIONS: Both Invisalign and conventional fixed appliances were effective in treating patients with a severe deep overbite. Invisalign therapy may be preferable over conventional fixed appliance therapy in patients with high angle and deep overbite. However, because this study had a retrospective design, the results should be viewed with caution.

Rehearsal's effect on long-term recall and comprehension of orthodontic informed consent.

INTRODUCTION: The purpose of this study was to determine if written rehearsal of informed consent improved 6-month recall and comprehension compared with the current best practices. METHODS: A consultation was provided and subjects read the modified informed consent document. They were randomized to group A (received the core and up to 4 custom elements of treatment, wrote what each image displayed) or group B (presentation of the 18 elements with core elements chunked at the end followed by up to 4 custom elements). Interviews recording knowledge recall/comprehension occurred immediately and after months later. RESULTS: Overall, no significant differences in baseline or 6-month follow-up scores were found between groups. Initially, group A outperformed group B in some core domains. There were no significant differences between groups in the change of scores from initial to follow-up. Follow-up scores were significantly lower than baseline scores (P <0.05). Higher initial scores were associated with larger drops at follow-up. A decrease in knowledge >20% was common. CONCLUSIONS: Overall the methods are comparable at baseline and 6-months. Initial content retention was roughly 60+%, with 6%-9% deterioration. For areas of treatment methods, risk, discomfort, and resorption at 6-months, the current processes failed the patient and left the practitioner vulnerable to risk management issues. Results support the rehearsal method with immediate feedback for misunderstandings as the preferred method for informed consent.

Comparison of 2 Invisalign tray generations using the Peer Assessment Rating index.

INTRODUCTION: This study aimed to establish if there is a significant difference in effectiveness between 2 generations of Invisalign trays in terms of Peer Assessment Rating (PAR) score reduction for finished patients from a graduate orthodontic clinic. METHODS: Forty-five pretreatment and posttreatment patients treated with the previous Invisalign material and 49 pretreatment and posttreatment patients treated with SmartTrack material were scored using the Peer Assessment Rating (PAR) index. Both groups were controlled for initial weighted PAR score, age, gender, and treatment time. The 2 generations were compared in regard to absolute reduction, percent reduction, and great improvement in PAR score. RESULTS: The mean absolute reduction in weighted PAR score between the groups was not statistically significant (P = 0.526). The mean percent reduction in weighted PAR score between the groups was not statistically significant (P = 0.210). The proportion of great improvement between the groups was not significant (P = 0.526). Only 6 of the 8 components of occlusion had enough variation to be modeled. An absolute reduction in unweighted PAR score was not significantly different between the groups for maxillary anterior alignment, overjet, or mandibular anterior alignment (P = 0.996, 1.000, and 0.114, respectively). Percent reduction in unweighted PAR score was not significantly different between the 2 groups for an anteroposterior, overbite, or transverse (P = 1.000, 1.000, and 1.000, respectively) relationships. CONCLUSIONS: Our study indicates that both generations of Invisalign aligners improved the malocclusion to a similar degree according to the PAR index. Patient-centric benefits of SmartTrack aligner should also be considered by the provider.

Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma.

Identification of prognostic factors for patients with relapsed/refractory Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase 2 study of positron emission tomography (PET)-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, and etoposide (augICE), we assessed clinical factors, quantitative PET assessments, and cytokine and chemokine values. Transplant-eligible patients with relapsed/refractory HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative patients (Deauville score ≤2) proceeded to autologous stem cell transplantation (ASCT) whereas PET-positive patients received augICE before ASCT. Serum cytokine and chemokine levels were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis were measured at baseline, after BV, and after augICE. Sixty-five patients enrolled (45, cohort 1; 20, cohort 2); 49 (75%) achieved complete response and 64 proceeded to ASCT. Three-year overall survival and event-free survival (EFS) were 95% and 82%, respectively. Factors predictive for EFS by multivariable analysis were baseline MTV (bMTV) (P < .001) and refractory disease (P = .003). Low bMTV (<109.5 cm3) and relapsed disease identified a favorable group (3-year EFS, 100%). For patients who received a transplant, bMTV and pre-ASCT PET were independently prognostic; 3-year EFS for pre-ASCT PET-positive patients with low bMTV was 86%. In this phase 2 study of PET-adapted therapy with BV and augICE for relapsed/refractory HL, bMTV and refractory disease were independent prognostic factors for EFS. Furthermore, bMTV improved the predictive power of pre-ASCT PET. Future studies should optimize efficacy and tolerability of salvage therapy by stratifying patients according to risk factors such as bMTV.

Role of imaging in low-grade cutaneous B-cell lymphoma presenting in the skin.

BACKGROUND: Whole-body imaging is the current standard of care for staging all patients presenting with skin lesions of B-cell lymphomas (BCLs), regardless of skin disease extent; however, supporting data are lacking. OBJECTIVE: To determine the clinical utility of imaging in the detection of systemic involvement in low-grade cutaneous BCLs in the skin. METHODS: Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center and Stanford University during 1997-2016. RESULTS: At initial staging, of the 522 patients, extracutaneous disease was noted in 3.6% and 8.8% of patients with marginal zone lymphoma (MZL, n = 306) and follicle center lymphoma (FCL, n = 216) histology, respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL cases and 89.4% of follicular lymphoma cases. In primary cutaneous MZL, 1.7% of patients subsequently had extracutaneous involvement (median follow-up 45 months), and in primary cutaneous FCL. 3.0% subsequently had extracutaneous involvement (median follow-up 47 months). LIMITATIONS: This was a retrospective study. CONCLUSION: Imaging is effective at identifying patients with systemic involvement in indolent BCLs present in the skin; however, incidence is low. After negative initial staging, primary cutaneous MZL patients may be followed clinically without routine imaging.

Outcomes of Relapsed and Refractory Primary Mediastinal (Thymic) Large B Cell Lymphoma Treated with Second-Line Therapy and Intent to Transplant.

Primary mediastinal (thymic) large B cell lymphoma is a subtype of diffuse large B cell lymphoma with distinct clinical, molecular, and genetic features, many of which overlap with Hodgkin lymphoma. Increasingly, initial therapy for these patients has used dose-dense chemotherapy with or without radiation with excellent results. In patients with relapsed and primary refractory disease, outcomes of second-line therapy followed by consolidation with high-dose therapy and autologous stem cell transplantation remains largely undefined. We reviewed the outcomes of 60 transplant-eligible patients with relapsed or refractory primary mediastinal (thymic) large B cell lymphoma enrolled on sequential protocols with uniform second-line therapy with intent to consolidate with autologous stem cell transplant. The estimated 3-year overall and event-free survivals for all patients were 61% and 57%, respectively, and 68% and 65%, respectively, for patients proceeding to stem cell transplant. Multivariable analysis of risk factors before transplant revealed that an incomplete response to initial therapy, advanced Ann Arbor stage at disease progression, and failure to achieve a partial remission or better to second-line therapy to be independently associated with inferior event-free and overall survival. A risk score based on these variables was able to identify patients who are unlikely to respond to conventional second-line strategies. These results suggest that salvage chemoradiotherapy with intent of subsequent high-dose therapy and autologous stem cell transplant is successful in most patients with relapsed and refractory primary mediastinal (thymic) large B cell lymphoma. Alternative strategies are warranted for a significant subset of patients with high-risk disease who are unlikely to be cured with this strategy.

Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial.

BACKGROUND: RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with lung cancers. To assess the activity of cabozantinib in patients with RET-rearranged lung cancers, we did a prospective phase 2 trial in this molecular subgroup. METHODS: We enrolled patients in this open-label, Simon two-stage, single-centre, phase 2, single-arm trial in the USA if they met the following criteria: metastatic or unresectable lung cancer harbouring a RET rearrangement, Karnofsky performance status higher than 70, and measurable disease. Patients were given 60 mg of cabozantinib orally per day. The primary objective was to determine the overall response (Response Criteria Evaluation in Solid Tumors version 1.1) in assessable patients; those who received at least one dose of cabozantinib, and had been given CT imaging at baseline and at least one protocol-specified follow-up timepoint. We did safety analyses in the modified intention-to-treat population who received at least one dose of cabozantinib. The accrual of patients with RET-rearranged lung cancer to this protocol has been completed but the trial is still ongoing because several patients remain on active treatment. This study was registered with ClinicalTrials.gov, number NCT01639508. FINDINGS: Between July 13, 2012, and April 30, 2016, 26 patients with RET-rearranged lung adenocarcinomas were enrolled and given cabozantinib; 25 patients were assessable for a response. KIF5B-RET was the predominant fusion type identified in 16 (62%) patients. The study met its primary endpoint, with confirmed partial responses seen in seven of 25 response-assessable patients (overall response 28%, 95% CI 12-49). Of the 26 patients given cabozantinib, the most common grade 3 treatment-related adverse events were lipase elevation in four (15%) patients, increased alanine aminotransferase in two (8%) patients, increased aspartate aminotransferase in two (8%) patients, decreased platelet count in two (8%) patients, and hypophosphataemia in two (8%) patients. No drug-related deaths were recorded but 16 (62%) patients died during the course of follow-up. 19 (73%) patients required dose reductions due to drug-related adverse events. INTERPRETATION: The reported activity of cabozantinib in patients with RET-rearranged lung cancers defines RET rearrangements as actionable drivers in patients with lung cancers. An improved understanding of tumour biology and novel therapeutic approaches will be needed to improve outcomes with RET-directed targeted treatment. FUNDING: Exelixis, National Institutes of Health and National Cancer Institute Cancer Center Support Grant P30 CA008748.

A cross-sectional study of demographic, environmental and parental barriers to active school travel among children in the United States.

BACKGROUND: Promoting daily routine physical activities, such as active travel to school, may have important health implications. Practitioners and policy makers must understand the variety of factors that influence whether or not a child uses active school travel. Several reviews have identified both inhibitors and promoters of active school travel, but few studies have combined these putative characteristics in one analysis. The purpose of this study is to examine associations between elementary school children's active school travel and variables hypothesized as correlates (demographics, physical environment, perceived barriers and norms). METHODS: The current project uses the dataset from the National Evaluation of Walk to School (WTS) Project, which includes data from 4th and 5th grade children and their parents from 18 schools across the US. Measures included monthly child report of mode of school travel during the previous week (n = 10,809) and perceived barriers and social norms around active school travel by parents (n = 1,007) and children (n = 1,219). Generalized linear mixed models (GLMM) with log-link functions were used to assess bivariate and multivariate associations between hypothesized correlates and frequency of active school travel, assuming random school effect and controlling for the distance to school. RESULTS: The final model showed that the most relevant significant predictors of active school travel were parent's perceived barriers, specifically child resistance (Estimate = -0.438, p < 0.0001) and safety and weather (Estimate = -0.0245, p < 0.001), as well as the school's percentage of Hispanic students (Estimate = 0.0059, p < 0.001), after adjusting for distance and including time within school cluster as a random effect. CONCLUSIONS: Parental concerns may be impacting children's use of active school travel, and therefore, future interventions to promote active school travel should more actively engage parents and address these concerns. Programs like the Walk to School program, which are organized by the schools and can engage community resources such as public safety officials, could help overcome many of these perceived barriers to active transport.

Pain Reduction of Ibuprofen Sodium Dihydrate Alone and in Combination with Acetaminophen in an Untreated Endodontic Pain Model: A Randomized, Double-blind Investigation.

INTRODUCTION: Most pain studies have been based on a postsurgical, third molar model using ibuprofen (IBU)/acetaminophen (APAP). Studies have found quicker onset of pain relief with a newer formulation of IBU - ibuprofen sodium dihydrate (ISD). The purpose of this study was to compare pain reduction of ISD/APAP to ISD in an acute endodontic pain model of untreated patients experiencing moderate to severe pain with symptomatic apical periodontitis. METHODS AND MATERIALS: In this double-blind randomized study, 64 adult emergency patients in acute moderate to severe pain, a pulpal diagnosis of symptomatic irreversible pulpitis or necrosis, and symptomatic apical periodontitis participated. Each patient randomly received either one dose of 768 mg ISD/1000 mg APAP or one dose of 768 mg ISD. Pain intensity scores were recorded every 15 minutes over 240 minutes using the Heft-Parker VAS along with time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief also recorded. The data were analyzed statistically. RESULTS: Both ISD and ISD/APAP groups showed a progressive decrease in pain from baseline to 120 minutes after medication administration. Afterward, a relative plateau was seen in the patients' pain. There was no difference in the VAS scores between the ISD and ISD/APAP at any given time point, time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief. CONCLUSIONS: The addition of APAP to ISD for pain control in an untreated endodontic pain model did not differ significantly from ISD alone.

Real-world treatment patterns of adjuvant endocrine therapy and ovarian suppression in premenopausal HR+/HER2+ breast cancer.

BACKGROUND: The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real-world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC. METHODS: This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti-HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use. RESULTS: Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients <35 years were more likely to receive OS compared with those ≥35 years (odds ratio 2.33, p < 0.001). CONCLUSIONS: This is the first real-world study evaluating ET treatment patterns in HR+/HER2+ premenopausal BC. OS use was uncommon and the majority received tamoxifen as the preferred ET regardless of most clinicopathologic risk factors. Additional research is needed to optimize ET decisions in young women with this distinct BC subtype.

A reference set of health utilities for long-term survivors of prostate cancer: population-based data from Ontario, Canada.

PURPOSE: To measure quality of life (QOL) and utilities for prostate cancer (PC) patients and determine their predictors. METHODS: A population-based, community-dwelling, geographically diverse sample of long-term PC survivors in Ontario, Canada, was identified from the Ontario Cancer Registry and contacted through their referring physician. Consenting patients completed questionnaires by mail: Health Utilities Index (HUI 2/3), Patient Oriented Prostate Utility Scale PORPUS-U (utility), PORPUS-P (health profile), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Prostate Cancer Index (PCI). Clinical data were obtained from chart reviews. Regression models determined the effects of a series of variables on QOL and utility. RESULTS: We received questionnaires and reviewed charts for 585 patients (mean age 72.6, 2-13 years postdiagnosis). Mean utility scores were as follows: PORPUS-U = 0.92, HUI2 = 0.85, and HUI3 = 0.78. Mean health profile scores were as follows: PORPUS-P = 71.7, PCI sexual, urinary, and bowel function = 23.7, 79.1, and 84.6, respectively (0 = worst, 100 = best), and FACT-P = 125.1 (0 = worst, 156 = best). In multiple regression analyses, comorbidity and PCI urinary, sexual, and bowel function were significant predictors of other QOL measures. With all variables, 32-50 % of the variance in utilities was explained. CONCLUSIONS: Many variables affect global QOL of PC survivors; only prostate symptoms and comorbidity have independent effects. Our model allows estimation of the effects of multiple factors on utilities. These utilities for long-term outcomes of PC and its treatment are valuable for decision/cost-effectiveness models of PC treatment.

Corticosteroids, behavior, and quality of life in children treated for acute lymphoblastic leukemia; a multicentered trial.

The aim of this study was to investigate the effects of high-dose corticosteroids on behavior and quality of life of children with acute lymphoblastic leukemia (ALL) in maintenance therapy. Forty-three families (patient and/or parent) completed the Child Behavior Checklist (CBCL), the Pediatric Quality of Life Inventory (PedsQL) Cancer module questionnaires, a checklist of common complaints, and a descriptive intervention data questionnaire, on and off steroids, each child serving as his/her own control. Children 5 years and younger had higher CBCL scores in the somatic complaints, affective problems, internalizing, externalizing, and total problem scales, when comparing "on-steroid" to "off-steroid" periods (P<0.01). Children 6 years and above had higher CBCL scores in the externalizing, aggressive, and oppositional defiant problem scales on steroids compared with off steroids (P<0.05). Older children had larger changes on dexamethasone, compared with prednisone (P<0.05). On the PedsQL questionnaire, parents reported more pain and hurt (P<0.001), nausea (P=0.042), and procedural anxiety (P=0.013) when children were on steroids compared with off steroids. Corticosteroid treatment during ALL maintenance therapy is associated with behavior and emotional disturbances and adversely affects quality of life. Dexamethasone is associated with more significant behavioral changes in older children.

The associations among economic hardship, caregiver psychological distress, disease activity, and health-related quality of life in children with juvenile idiopathic arthritis.

PURPOSE: To examine the associations among caregiver perceived economic hardship, psychological distress, children's disease activity, and health-related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA). METHODS: Caregivers of 182 children with JIA (ages 2-18) attending the rheumatology clinics at the Montreal Children's Hospital and the British Columbia's Children Hospital completed a series of questionnaires on perceived financial hardship, caregiver psychological distress, and children's HRQOL at baseline, 6 and 12 months. Clinical information such as disease activity was obtained from medical charts. Statistical models were used to look at the significance of several factors of interest while controlling for possible confounders. RESULTS: Higher caregiver perceived economic hardship [(ß = 0.03, 95% CI = 0.005, 0.06), P = 0.02], psychological distress [(ß = 0.02, 95% CI = 0.006, 0.03), P = 0.004], and higher children's disease activity [(ß = 0.11, 95% CI = 0.07, 0.15), P < 0.0001] were associated with worse children's HRQOL. CONCLUSIONS: Findings suggest that caregiver financial hardship and psychological distress as well as children's disease activity may impact children's HRQOL. By providing psychological help to parents, offering information regarding financial resources in the community and by ensuring disease control, especially when the disease is severe, health providers may improve children's health outcomes.

Lung volume recruitment slows pulmonary function decline in Duchenne muscular dystrophy.

OBJECTIVE: To evaluate the long-term effect on measures of forced vital capacity (FVC) before and after the introduction of regular lung volume recruitment (LVR) maneuvers (breath-stacking) in individuals with Duchenne muscular dystrophy (DMD). DESIGN: Retrospective cohort study of pulmonary function data, including FVC, cough peak flow (CPF), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP). Data were collected for 33 months prior to and 45 months after LVR introduction. SETTING: Ambulatory care in a tertiary level regional rehabilitation center in Canada. PARTICIPANTS: All individuals (N=22) with DMD (mean age ± SD, 19.6±2.4y), who were prescribed LVR and reported adherence with therapy. INTERVENTIONS: Introduction of regular LVR (breath-stacking); 3 to 5 maximal lung inflations (maximum insufflation capacity [MIC]) using a hand-held resuscitation bag and mouthpiece, twice daily. MAIN OUTCOME MEASURES: Measures included the rate of decline of FVC in percent-predicted, before and after the introduction of regular LVR. Changes in maximum pressures (MIP, MEP), MIC, and cough peak flows were also measured. RESULTS: At LVR initiation, FVC was 21.8±16.9 percent-predicted, and cough peak flows were <270L/min (144.8±106.9L/min). Annual decline of FVC was 4.7 percent-predicted a year before LVR and 0.5 percent-predicted a year after LVR initiation. The difference, 4.2 percent-predicted a year (95% confidence interval, 3.5-4.9; P<.000), represents an 89% improvement in the annual rate of FVC decline. CONCLUSIONS: The rate of FVC decline in DMD patients improves dramatically with initiation of regular LVR.

Referral rate for obstructive sleep apnea in a pre-doctoral dental clinic using the STOP-Bang Questionnaire.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common condition that can result in significant illness when untreated. Only 10%-20% of individuals with OSA are believed to be properly diagnosed. Consequently, dentists are encouraged to identify patients at high risk for OSA. The aim of this study was to determine whether patients in a dental school student clinic were referred for evaluation of OSA when appropriate. MATERIALS AND METHODS: All patients 18 or older admitted to the College of Dentistry between July 2017 and March 2020 completed a medical history form. Data were extracted from their responses to determine a STOP-Bang score, as well as data regarding a previous diagnosis of OSA and a list of referrals. Students are expected to refer patients appropriately where there are indications of a high risk of undiagnosed disease. In the case of a sleep apnea evaluation, this would include any patient whose STOP-Bang score was 5 or greater, per the lecture on sleep disorders. For patients identified as high risk, notes and referral forms were reviewed to determine if the appropriate referral occurred. RESULTS: Of the 21,312 new patients, 1098 (5.2%) were identified as high-risk for OSA. Of those, 398 (36%) had not been previously diagnosed with OSA. None of these 398 patients received a referral for further evaluation of OSA. CONCLUSION: The rate of referral for further evaluation for patients deemed at high risk for OSA was inadequate. Continued education and changes to the electronic health record are needed to ensure those at high-risk for OSA are appropriately managed.

The impact of anti-CD20-based therapy on hypogammaglobulinemia in patients with follicular lymphoma.

Although treatment with anti-CD20 monoclonal antibodies (mAb) has improved outcomes in B-cell malignancies, it's associated with increased risk of hypogammaglobulinemia (HG). Our study aimed to determine the effects of anti-CD20 mAb on serum immunoglobulins (Ig) in follicular lymphoma (FL). Ig concentrations, infectious complications, and need for intravenous Ig were evaluated by level of exposure to anti-CD20 mAb in 380 patients. Prevalence of HG significantly differed by level of treatment exposure (p < 0.001). Single course anti-CD20 mAb was associated with rising IgG (+10.3 mg/dL/year), whereas the addition of maintenance therapy (-7.4 mg/dL/year) or multiple courses of treatment (-10.3 mg/dL/year) was associated with declining IgG. Among patients treated with anti-CD20 mAb, 45.2% developed IgG-HG and 10.3% developed symptomatic IgG-HG. Pretreatment IgG levels gradually declined in all patients, suggesting tumor burden may contribute to HG. Baseline and periodic monitoring of serum Ig is appropriate in patients with FL, including those managed with active surveillance.

Phase 1 Clinical Trial of Trametinib and Ponatinib in Patients With NSCLC Harboring KRAS Mutations.

INTRODUCTION: Somatic KRAS mutations occur in 25% of patients with NSCLC. Treatment with MEK inhibitor monotherapy has not been successful in clinical trials to date. Compensatory activation of FGFR1 was identified as a mechanism of trametinib resistance in KRAS-mutant NSCLC, and combination therapy with trametinib and ponatinib was synergistic in in vitro and in vivo models. This study sought to evaluate this drug combination in patients with KRAS-mutant NSCLC. METHODS: A phase 1 dose escalation study of trametinib and ponatinib was conducted in patients with advanced NSCLC with KRAS mutations. A standard 3-plus-3 dose escalation was done. Patients were treated with the study therapy until intolerable toxicity or disease progression. RESULTS: A total of 12 patients with KRAS-mutant NSCLC were treated (seven at trametinib 2 mg and ponatinib 15 mg, five at trametinib 2 mg and ponatinib 30 mg). Common toxicities observed were rash, diarrhea, and fever. Serious adverse events potentially related to therapy were reported in five patients, including one death in the study and four cardiovascular events. Serious events were observed at both dose levels. Of note, 75% (9 of 12) were assessable for radiographic response and no confirmed partial responses were observed. The median time on study was 43 days. CONCLUSIONS: In this phase 1 study, in patients with KRAS-mutant advanced NSCLC, combined treatment with trametinib and ponatinib was associated with cardiovascular and bleeding toxicities. Exploring the combination of MEK and FGFR1 inhibition in future studies is potentially warranted but alternative agents should be considered to improve safety and tolerability.