Immune-related adverse effects: Recognition and initiation of appropriate treatment in cancer patients on immunotherapy.

PURPOSE: Delayed or improper identification of immune-related adverse events (IRAEs) during cancer treatment can impact time to receive proper treatment. This study describes rates of IRAE recognition and appropriate treatment in adult patients with cancer at a community teaching hospital. METHODS: This single-center, retrospective, cohort study evaluated rates of proper IRAE treatment in conjunction with National Comprehensive Cancer Network (NCCN) guidelines. Secondary outcomes included time from presentation to IRAE diagnosis and hospital readmissions/repeat emergency department (ED) visits following initial admission for IRAE. Retrospective chart review assessed IRAE presentation including common terminology criteria for adverse event (CTCAE) grading and treatment choices. RESULTS: Fifteen subjects included in this study contributed to 21 encounters with noted IRAE. Over half (52.4%) of the encounters received proper IRAE treatment (e.g. correct drug, dose, route, frequency, or therapy duration). Nearly 22% of total actionable components were improper, occurring more often in patients with colitis, pneumonitis, and hepatitis. Median time to IRAE diagnosis was approximately 3.5 days, with the longest being 24 days. There were eight all-cause rehospitalizations one year after initial IRAE presentation, with four directly IRAE-related. Most (75%) IRAE-related rehospitalizations occurred with colitis. Seven ED return visits were also noted. CONCLUSION: Many IRAEs were misdiagnosed and/or received improper treatment resulting in increased rehospitalization/return ED visit rates. The importance of medical oncology involvement (e.g. medical oncology consult at time of admission and/or notification of primary oncologist) in IRAE management in the hospital or ED was also stressed. Organizations may benefit from systematic improvements and staff education to improve patient outcomes and prevent readmissions.

Implementation of an interprofessional education program in a community teaching hospital and its impact on student perceptions of other healthcare professions.

In this single-center, prospective study we evaluated the impact of an interprofessional education program (IPE) on healthcare students' perceptions of other healthcare professions. The program consisted of four one-hour, roundtable, case-based sessions with students and several facilitators from medicine, nursing, pharmacy, and physician assistant programs. Included students were 18 years of age or older and currently enrolled in a healthcare program during the study time frame. The primary outcome of student perceptions of other healthcare professions was measured by baseline and follow-up surveys using the Adapted Attitudes Toward Interprofessional Health Care Teams scale. Perceptions of students who participated in the IPEP (intervention group) were compared to similar healthcare program students who did not participate in the program (control group). Overall, the intervention group had significantly higher perceptions of other healthcare professions comparing pre-intervention to post -intervention data (pre-intervention mean ± SD of 57.2 ± 5.24; post-intervention mean 60.7 ± 5.63; p = .02). This improvement in perceptions was also seen when comparing the post-intervention group to the control group (control mean 56.7 ± 5.1; post-intervention mean 60.7 ± 5.63; p = .008).

Acute effects of interrupting prolonged sitting on vascular function in type 2 diabetes.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: 1) uninterrupted sitting (SIT), 2) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D.NEW & NOTEWORTHY This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.

Self-compassion predicts less fear of childbirth in childless women: the mediating role of birth beliefs.

OBJECTIVE: Women can have fear of childbirth (FOC) in advance of their first pregnancy and such fear can have implications for reproductive and eventual childbirth choices. This study aims to further our understanding of the role of self-compassion in FOC in young childless women, including possible pathways through which self-compassion might relate to less FOC: through natural and medical birth beliefs. DESIGN AND MAIN OUTCOME MEASURES: In this correlational study, 316 young childless Australian women completed measures of self-compassion, natural and medical birth beliefs, and FOC. RESULTS: Self-compassion predicted less FOC, and although self-compassion as a total score did not relate to natural birth beliefs, it did relate to lower scores on medical birth beliefs. The indirect effect through medical birth beliefs was supported; greater self-compassion predicted lower scores on medical birth beliefs, which in turn predicted less FOC. CONCLUSIONS: The findings, although cross-sectional, support the study of self-compassion in FOC, which is in part because self-compassion predicts less medical birth beliefs. With further research, self-compassion training might be incorporated into public health initiatives targeting FOC in young childless women.

Interrupting Prolonged Sitting and Endothelial Function in Polycystic Ovary Syndrome.

PURPOSE: In healthy adults, the impairment of vascular function associated with prolonged sitting can be mitigated with intermittent brief bouts of activity. It is unknown whether these benefits extend to women with polycystic ovary syndrome (PCOS), in whom vascular function is typically impaired and sitting time is high. We examined the acute effect of regularly interrupting sitting time with brief simple resistance activities (SRA) on vascular function in PCOS. METHODS: In a randomized crossover trial, 13 physically inactive women with PCOS (18-45 yr) completed two 3.5-h conditions: 1) uninterrupted sitting (SIT) and 2) sitting interrupted by 3-min bouts of SRA every 30 min. Femoral artery flow-mediated dilation (FMD), resting shear rate, and resting blood flow were measured at 0, 1, and 3.5 h. RESULTS: Mean resting femoral shear rate, averaged across the 3.5 h, significantly increased in the SRA condition relative to the SIT condition (40.1 ± 6.1 vs 62.8 ± 6.1 s-1, P < 0.0001). In addition, mean resting blood flow also significantly increased across the 3.5 h for SRA relative to SIT (45.0 ± 9.8 vs 72.8 ± 9.9 mL·min-1, P < 0.0001). There were no differences between conditions in the temporal change in femoral artery FMD across 3.5 h (Ptime-condition > 0.05 for all). CONCLUSION: Frequently interrupting sitting with SRA acutely increased resting shear rate and blood flow in women with PCOS but did not alter FMD. With sedentary behavior increasing in prevalence, longer-term studies of similar interventions to reduce and break up sitting time are warranted.

Frequency of Interruptions to Sitting Time: Benefits for Postprandial Metabolism in Type 2 Diabetes.

OBJECTIVE: To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin, and triglycerides in adults with medication-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Participants (n = 23, 10 of whom were female, with mean ± SD age 62 ± 8 years and BMI 32.7 ± 3.5 kg · m-2) completed a three-armed randomized crossover trial (6- to 14-day washout): sitting uninterrupted for 7 h (SIT), sitting with 3-min SRAs (half squats, calf raises, gluteal contractions, and knee raises) every 30 min (SRA3), and sitting with 6-min SRAs every 60 min (SRA6). Net incremental areas under the curve (iAUCnet) for glucose, insulin, and triglycerides were compared between conditions. RESULTS: Glucose and insulin 7-h iAUCnet were attenuated significantly during SRA6 (glucose 17.0 mmol · h · L-1, 95% CI 12.5, 21.4; insulin 1,229 pmol · h · L-1, 95% CI 982, 1,538) in comparison with SIT (glucose 21.4 mmol · h · L-1, 95% CI 16.9, 25.8; insulin 1,411 pmol · h · L-1, 95% CI 1,128, 1,767; P < 0.05) and in comparison with SRA3 (for glucose only) (22.1 mmol · h · L-1, 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUCnet were observed in comparison of SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUCnet. CONCLUSIONS: In adults with medication-controlled T2D, interrupting prolonged sitting with 6-min SRAs every 60 min reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance.

Predictors of swallow function after transoral surgery for locally advanced oropharyngeal cancer.

OBJECTIVE: Transoral surgery (TOS) for oropharyngeal carcinoma (OPC) is steadily becoming more routine. Expected posttreatment swallow function is a critical consideration for preoperative counseling. The objective of this study was to identify predictors of swallow dysfunction following TOS for advanced tumor (T)-stage (T3-T4) OPC. METHODS: A retrospective review from 1997 to 2016 at a single institution was performed. Eighty-two patients who underwent primary transoral resection of locally advanced OPCs with at least 1 year of postoperative follow-up were included. The primary outcome measure was swallow function, as measured by the Functional Outcomes Swallowing Scale (FOSS) at 1 year postoperatively. Operative reports were reviewed, and the extent of resection and type of reconstruction were documented. Conjunctive consolidation was then performed to incorporate multiple variables and their impact on swallow function into a clinically meaningful classification system. RESULTS: Fifty-six patients (68%) had acceptable swallowing at 1 year. T4 tumor stage and receipt of adjuvant chemoradiation therapy (CRT) were strongly associated with poor swallowing but did not reach statistical significance. Only base of tongue (BOT) resection ≥50% (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.21-8.43) and older age (OR 1.06, 95% CI 1.00-1.12) were significantly associated. Utilizing T-stage, adjuvant CRT, and BOT resection, a conjunctive consolidation was performed to develop a classification system for swallow dysfunction at 1 year. CONCLUSION: This study provides risk stratification for swallow function at 1 year following primary transoral resection of locally advanced OPCs. BOT resection ≥50%, especially when coupled with T4 tumor stage or adjuvant CRT, was associated with poor long-term swallow outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:94-100, 2020.

Timing of Postoperative Radiotherapy in Surgically Treated HPV-Positive Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Optimal timing of postoperative radiotherapy (PORT) remains understudied in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma. Objectives are to determine if delays between surgery and radiotherapy, breaks during radiotherapy, disease, or patient factors are associated with recurrence or survival decrements in HPV-related disease. DESIGN: Retrospective review. SETTING: Academic medical center. SUBJECTS: A total of 240 cases of HPV-positive oropharyngeal squamous cell carcinoma from 2000 to 2016. METHODS: Patient and tumor characteristics (American Joint Committee on Cancer, eighth edition), delays to radiation initiation, and breaks during radiation were recorded. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. RESULTS: RFS and OS were not significantly affected by delays to PORT >6 weeks or by treatment intervals >100 days (surgery to PORT completion). Breaks during PORT significantly imparted an OS detriment (hazard ratio [HR], 2.4; 95% CI, 1.2-4.8). Advanced-stage disease was significantly associated with reduced RFS and OS. Subgroup analysis of stage I versus stage II/III disease found that >6 weeks to PORT initiation and treatment intervals >100 days did not significantly decrease RFS or OS in either stage group. Advanced-stage disease was significantly associated with worsened OS (HR, 6.6; 95% CI, 2.3-19.1) and RFS (HR, 5.3; 95% CI, 1.5-18.4). Breaks during PORT significantly reduced RFS (HR, 3.6; 95% CI, 1.2-10.8) and OS (HR, 3.2; 95% CI, 1.2-9.0) in the stage II/III subset. CONCLUSION: Delays to radiotherapy initiation and prolonged treatment time did not affect recurrence or survival in HPV-related oropharyngeal disease. Locoregionally advanced disease was consistently associated with worse outcomes. Breaks during PORT may affect recurrence and survival, although larger studies are needed to confirm this finding.

Effect of Perioperative Gabapentin Use on Postsurgical Pain in Patients Undergoing Head and Neck Mucosal Surgery: A Randomized Clinical Trial.

Importance: Effective postoperative pain management increases patient satisfaction, reduces cost, reduces morbidity, and shortens hospitalizations. Previous studies investigating multimodal pain therapy in otolaryngology patients focused on homogenous patient groups with short postoperative follow-up times. Objective: To investigate the effect of perioperative gabapentin treatment on postsurgical pain in patients undergoing head and neck mucosal surgery. Design, Setting, and Participants: Adults undergoing head and neck mucosal surgery from July 25, 2016, through June 19, 2017, were included in this double-blinded, placebo-controlled randomized clinical trial and randomized to receive gabapentin, 300 mg twice daily, or placebo before surgery and up to 72 hours after surgery. Main Outcomes and Measures: Primary outcome was hourly narcotic use calculated in morphine equivalents. Secondary outcomes included subjective visual analog scale pain scores captured for resting, coughing, and swallowing using a 0- to 100-mm scale (a 100-mm line anchored with no pain on the left end and worst possible pain on the right end). A change of 10 mm or more was deemed to be clinically meaningful. Additional secondary outcome measures included degree of pain control, patient satisfaction, and adverse effects. Results: Of the 110 patients randomized to receive gabapentin or placebo, 11 and 10 withdrew from each group, respectively. Ninety patients were then analyzed: 44 in the gabapentin group (mean [SD] age, 61.1 [10.0] years; 33 [75%] male; 40 [91%] white) and 46 in the placebo group (mean [SD] age, 60.9 [11.3] years; 35 [78%] male; 43 [94%] white). Both groups had similar self-reported levels of preoperative pain and narcotic effectiveness. A median difference of 0.26 mg/h of morphine (95% CI, -0.27 to 0.94 mg/h) was found between groups. After controlling for comorbidity and self-reported baseline pain levels, mixed model analysis found the difference in marginal means of visual analog scale scores between groups to be lower in the gabapentin group compared with the placebo group for all categories (rest difference, 7.9 mm; 95% CI, -0.4 to 16.2 mm; cough difference, 8.9 mm; 95% CI, -0.5 to 18.3 mm; swallow difference, 9.4 mm; 95% CI, -1.2 to 20.0 mm). More patients in the gabapentin group reported that pain was always well controlled than in the placebo group (difference, 9.2%; 95% CI, -21% to 3%). Gabapentin and placebo groups reported similar levels of satisfaction with pain control (difference, 2%; 95% CI, -11% to 15%). There was no clinically meaningful difference in reported nausea between the 2 groups (difference, 6%; 95% CI, -14% to 26%). Conclusion and Relevance: Perioperative gabapentin given 300 mg twice daily did not result in reduced narcotic use, but results were compatible with clinically meaningful reductions in pain scores. Satisfaction with pain control and adverse effects were similar between groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02926573.

The P Value Problem in Otolaryngology: Shifting to Effect Sizes and Confidence Intervals.

There is a lack of reporting effect sizes and confidence intervals in the current biomedical literature. The objective of this article is to present a discussion of the recent paradigm shift encouraging the use of reporting effect sizes and confidence intervals. Although P values help to inform us about whether an effect exists due to chance, effect sizes inform us about the magnitude of the effect (clinical significance), and confidence intervals inform us about the range of plausible estimates for the general population mean (precision). Reporting effect sizes and confidence intervals is a necessary addition to the biomedical literature, and these concepts are reviewed in this article.

Evaluation of Quality Metrics for Surgically Treated Laryngeal Squamous Cell Carcinoma.

Importance: Quality metrics for patients with laryngeal squamous cell carcinoma (SCC) exist, but whether compliance with these metrics correlates with improved survival is unknown. Objective: To examine whether compliance with proposed quality metrics is associated with improved survival in patients with laryngeal SCC treated with surgery with or without adjuvant therapy. Design, Setting, and Participants: This retrospective cohort study included patients from a tertiary care academic medical center who had previously untreated laryngeal SCC and underwent surgery with or without adjuvant therapy from January 1, 2003, through December 31, 2012. Data analysis was performed from August 4, 2015, through December 13, 2015. Interventions: Surgery with or without adjuvant therapy. Main Outcomes and Measures: Compliance with quality metrics from the American Head and Neck Society (AHNS), National Comprehensive Cancer Network (NCCN) guidelines, and institutional metrics with face validity covering pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. The association between compliance with the group of metrics and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) was explored using Cox proportional hazards analysis. The association between compliance with individual metrics and survival was similarly determined. Results: A total of 243 patients (184 men and 59 women) were included in the study (median age, 62 years; age range, 23-87 years). No association was found between increasing levels of compliance with the AHNS or NCCN metrics and survival. The only AHNS or NCCN metric for which greater compliance correlated with improved survival on multivariable Cox proportional hazards analysis controlling for pT stage, pN stage, extracapsular spread, margin status, and comorbidity was pretreatment multidisciplinary evaluation for patients with stage cT3-4 or cN1-3 disease (OS adjusted hazard ratio [aHR], 0.47; 95% CI, 0.24-0.94; DFS aHR, 0.45; 95% CI, 0.23-0.85). For the institutional metrics, multidisciplinary evaluation for all patients (OS aHR, 0.51; 95% CI, 0.29-0.88; DFS aHR, 0.50, 95% CI, 0.32-0.80) and elective neck dissection yield of 18 lymph nodes or more (DFS aHR, 0.36; 95% CI, 0.14-0.99) were associated with improved survival on multivariable Cox proportional hazards analysis. Conclusions and Relevance: In this cohort of patients with surgically treated laryngeal SCC, multidisciplinary evaluation and elective neck dissection yield of 18 lymph nodes or more are associated with improved survival. Development of better quality metrics is necessary because increased compliance with metrics described by the AHNS and NCCN is not associated with improved survival. Previously described metrics for surgically treated oral cavity cancer are not prognostic for surgically treated laryngeal SCC. Future multi-institutional collaboration will be required to validate these findings, develop better quality metrics, and evaluate whether quality metrics for head and neck cancer are site specific.

Transcriptional activation of the tyrosine phosphatase gene, OST-PTP, during osteoblast differentiation.

Protein tyrosine phosphatases (PTPs) are critical regulators of cellular phosphorylation functioning in processes such as cell growth, differentiation, and adhesion. Osteotesticular PTP (OST) is the only characterized member of this superfamily whose expression is regulated in osteoblasts and critical for their in vitro differentiation. Such evidence would suggest that this molecule is a key modulator of signaling events during osteogenesis, yet little is known about its genetic regulation. In an effort to examine the molecular mechanisms involved in the cellular regulation of OST, we have characterized its expression in MC3T3 osteoblasts during differentiation. Northern analysis revealed that murine OST mRNA is dramatically regulated during the preosteoblast to osteoblast progression, with predominant expression in differentiated and early mineralizing osteoblasts. This expression pattern is unique to this phosphatase since, in comparison, the structurally similar receptor PTP, LAR, and the intracellular PTP1B show little change during differentiation. Cell density contributes to this upregulated expression as confluent cultures display an increase in OST transcripts within 4 h post-plating. Transient transfection of the OST promoter in differentiating MC3T3 results in a significant increase in transcriptional activation from day 0 to day 5 of differentiation, similar in timing and intensity to the observed upregulation of the endogenous gene. This activation appears to be specific to osteoblasts, since progression to a myoblast phenotype results in no change in reporter gene activity. Culturing these preosteoblast cells in the absence of critical co-factors results in an inhibition of differentiation and leads to a delayed induction of OST transcripts as well as the attenuation of transcriptional activation. These results show that the murine OST gene is regulated at the transcriptional level in an osteoblast-specific, differentiation-dependent manner during the differentiation of MC3T3 osteoblasts. Future studies will help determine the essential regulatory elements within the OST-PTP promoter and the critical signaling pathways important in this regulation.