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OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ± 12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.

It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from those of other anti-cancer agents, occur with regularity, and impact patient outcomes. mIAS pathogenesis has been the subject of speculation, and its similar presentation to recurrent aphthous stomatitis (RAS) has led to the hypothesis that it might serve as a surrogate to better understand RAS. Based on a review of the literature, the current manuscript provides a hypothesis regarding the mechanisms by which mTORis uniquely initiate mucosal injury and an explanation for the observation that steroids (also an immunosuppressive) are effective in its treatment through a non-immunologic mechanism. Unexplained unique features of mIAS are discussed in this review in the context of future investigation.

The article provides a comparative analysis of reparative osteogenesis in 105 patients with diffuse osteomyelitis of lower extremities, covering bone in diameter totally or subtotally. In complex treatment 51 patients have experienced gravitational therapy (study group), 54 patients have been treated by standard methods (control group). The study was conducted in clinics of Samara State Medical University. Gravitational therapy is a new noninvasive method of physiotherapy, first used in the treatment of patients with osteomyelitis. It is noted that the inclusion of gravitational therapy in complex treatment contributes to the consolidation of bone fragments, accelerates о ste о reparative processes in the regenerate bone formed in the zone of the defect in osteosynthesis in apparatus for external fixation. Past radionuclide study of the skeleton showed that the gravitational therapy positively affects the blood supply to the area osteomyelitic defeat, activates and improves bone metabolism. Osteodensimetric studies have shown that under the influence of gravitational therapy there was an increase in bone mineral density of the lower extremities, especially with the affected side, which was not observed in patients of control group. Gravitational therapy is an effective method of influence on reparative osteogenesis in patients with osteomyelitis of lower extremities

Introduction: While emergency department (ED) crowding has deleterious effects on patient care outcomes and operational efficiency, impacts on the experience for patients discharged from the ED are unknown. We aimed to study how patient-reported experience is affected by ED crowding to characterize which factors most impact discharged patient experience. Methods: This institutional review board-exempt, retrospective, cohort study included all discharged adult ED patients July 1, 2020–June 30, 2021 with at least some response data to the the National Research Corporation Health survey, sent to most patients discharged from our large, academic medical center ED. Our query yielded 9,401 unique encounters for 9,221 patients. Based on responses to the summary question of whether the patient was likely to recommend our ED, patients were categorized as “detractors” (scores 0-6) or “non-detractors” (scores 7-10). We assessed the relationship between census and patient experience by 1) computing percentage of detractors within each care area and assessing for differences in census and boarder burden between detractors and non-detractors, and 2) multivariable logistic regression assessing the relationship between likelihood of being a detractor in terms of the ED census and the patient’s last ED care area. A second logistic regression controlled for additional patient- and encounter-specific covariates.  Results: Survey response rate was 24.8%. Overall, 13.9% of responders were detractors. There was a significant difference in the average overall ED census for detractors (average 3.70 more patients physically present at the time of arrival, 95% CI 2.33- 5.07). In unadjusted multivariable analyses, three lower acuity ED care areas showed statistically significant differences of detractor likelihood with changes in patient census. The overall area under the curve (AUC) for the unadjusted model was 0.594 (CI 0.577-0.610). The adjusted model had higher AUC (0.673, CI 0.657- 0.690]; P

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

The incidence of oropharyngeal cancer (OPC) has been rising, especially among middle-aged men. While Human Papillomavirus (HPV) has been irrevocably implicated in the pathogenesis of oropharyngeal cancer (OPC), the current HPV vaccination uptake rate remains low in the US. The aim of our study was to evaluate the impact of increased HPV vaccination coverage on HPV-associated OPC incidence and costs. A decision analytic model was constructed for hypothetical cohorts of 9-year-old boys and girls. Two strategies were compared: 1) Maintaining the current vaccination uptake rates; 2) Increasing HPV vaccination uptake rates to the Healthy People 2030 target (80%) for both sexes. Increasing HPV vaccination coverage rates to 80% would be expected to prevent 5,339 OPC cases at a cost of $0.57 billion USD. Increased HPV vaccination coverage would result in 7,430 quality-adjusted life year (QALY) gains in the overall population, and it is estimated to be cost-effective for males with an incremental cost-effectiveness ratio of $86,940 per QALY gained under certain conditions. Expanding HPV vaccination rates would likely provide a cost-effective way to reduce the OPC incidence, particularly among males.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of antineoplastic therapy that restore anti-tumor immunity. Consequences of this enhanced immune response include a multitude of immune related adverse events (irAEs) that can affect any body system, including the mouth. Orofacial irAEs reproduce features of numerous immune-mediated conditions, including oral lichen planus, mucous membrane pemphigoid, and Sjögren syndrome, among others. The aim of this review is to summarize known orofacial irAEs and to familiarize oral healthcare providers with how to identify and manage these toxicities as part of the care team for patients treated with ICIs.

Abstract Photobiomodulation therapy (PBMT) is recommended for prevention and treatment of oral mucositis, a painful condition that occurs in cancer patients. Intraoral PBMT is limited to treating distal oral mucosa and oropharynx. Extraoral PBMT may provide a more efficient intervention. The goal of this study was to develop a clinically viable protocol for extraoral PBMT. Monte Carlo modeling was used to predict the distribution of 850 nm light for four treatment sites, using anatomical data obtained from MRI and optical properties from the literature. Simulated incident light power density was limited to 399 mW/cm2 to ensure treatment safety and to prevent tissue temperature increase. The results reveal that total tissue thickness determines fluence rate at the oral mucosa, whereas the thickness of individual tissue layers and melanin content are of minor importance. Due to anatomical differences, the fluence rate varied greatly among patients. Despite these variations, a universal protocol was established using a median treatment time methodology. The determined median treatment times required to deliver efficacious dose between 1 and 6 J/cm2 were within 15 min. The developed PBMT protocol can be further refined using the combination of pretreatment imaging and the Monte Carlo simulation approach implemented in this study.

IntroductionThe negative consequences of healthcare-associated infections (HAI) on the burden of illness (BOI) of cancer patients are well-established. However, there is a paucity of research on HAI among cancers of the lip, oral cavity and pharynx (CLOCP), and whether HAI-related BOI differed for other common solid tumors-malignant neoplasm of the colon (MNC) and malignant neoplasm of the lung (MNL).MethodsWe utilized the United States' National Inpatient Sample database 2017 to study longitudinal inpatient hospital stay of CLOCP, MNC and MNL. Patient demographics and hospital characteristics of patients were assessed, and the impact of HAI-related BOI compared based on differences in length of hospital stays (LOS), total charges during hospitalization and mortality were compared.FindingsIn 2017, of the 54,934 patients with CLOCP, 1.2% had HAI, compared to MNC (n=64,470) with 2% HAI and MNL (n=154,685) with 1.2% HAI. In adjusted multivariable regression analysis, we determined CLOCP patients with HAI had LOS of 5.6 days longer (95% CIs, 3.0-8.2 days, P < 0.001), and hospitalization charges of $40,341 higher (95%CIs 15,715-64,967, P < 0.01) than the non-HAI CLOCP patients. Mortality was not significantly different among HAI and non-HAI CLOCP patients (odds ratio: 0.80; 95%CIs 0.35-1.87, P = 0.6). In unadjusted analysis, LOS and total charges were higher for CLOCP-HAI patients vs. MNC-HAI or MNL-HAI patients.ConclusionHAI in patients with CLOCP patients were associated with an increased BOI, and this is considerably higher than observed in patients with MNC or MNL patients who had HAI.

The global COVID-19 pandemic has become one of the largest clinical and operational challenges faced by emergency medicine, and our EDs continue to see increased volumes of infected patients, many of whom are not only ill, but acutely aware and fearful of their circumstances and potential mortality. Given this, there may be no more important time to focus on staff-patient communication and expression of compassion.However, many of the techniques usually employed by emergency clinicians to provide comfort to patients and their families are made more challenging or impossible by the current circumstances. Geriatric ED patients, who are at increased risk of severe disease, are particularly vulnerable to the effects of isolation.Despite many challenges, emergency clinicians have at their disposal a myriad of tools that can still be used to express compassion and empathy to their patients. Placing emphasis on using these techniques to maximize humanism in the care of COVID-19 patients during this crisis has the potential to bring improvements to ED patient care well after this pandemic has passed.

Abstract Objective To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). Materials and methods A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. Results Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. Conclusion Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

We performed a retrospective cohort study of patients admitted to a novel, home-based COVID Virtual Observation Unit (CVOU) from an urban, university-affiliated emergency department with ∼112,000 annual visits. Telephone-based survey questions were administered by nursing staff working with the program. Of 402 patients enrolled in the CVOU, 221 (55%) were able to be contacted during the study period; 180 (45%) agreed to participate in the telephone interview. Overall, 95% (169 out of 177) of the surveyed patients reported 8 to 10 on the likelihood to recommend CVOU and 82% (100 out of 122) rated the quality of care as 10 out of 10. Over 90% of respondents reported that all role groups (nurses, paramedics, and physicians) treated them with courtesy and respect, explained things in an understandable way, and listened to them carefully. Over 80% of respondents reported that the program kept them at home. In summary, patient experiences with this novel home-based care program were highly positive. These data help underscore the importance of patient-centeredness in home-based care, and further support the concept of these innovative care models.

Introduction: While emergency department (ED) crowding has deleterious effects on patient care outcomes and operational efficiency, impacts on the experience for patients discharged from the ED are unknown. We aimed to study how patient-reported experience is affected by ED crowding to characterize which factors most impact discharged patient experience. Methods: This institutional review board-exempt, retrospective, cohort study included all discharged adult ED patients July 1, 2020–June 30, 2021 with at least some response data to the the National Research Corporation Health survey, sent to most patients discharged from our large, academic medical center ED. Our query yielded 9,401 unique encounters for 9,221 patients. Based on responses to the summary question of whether the patient was likely to recommend our ED, patients were categorized as “detractors” (scores 0–6) or “non-detractors” (scores 7–10). We assessed the relationship between census and patient experience by 1) computing percentage of detractors within each care area and assessing for differences in census and boarder burden between detractors and non-detractors, and 2) multivariable logistic regression assessing the relationship between likelihood of being a detractor in terms of the ED census and the patient’s last ED care area. A second logistic regression controlled for additional patient- and encounter-specific covariates. Results: Survey response rate was 24.8%. Overall, 13.9% of responders were detractors. There was a significant difference in the average overall ED census for detractors (average 3.70 more patients physically present at the time of arrival, 95% CI 2.33–5.07). In unadjusted multivariable analyses, three lower acuity ED care areas showed statistically significant differences of detractor likelihood with changes in patient census. The overall area under the curve (AUC) for the unadjusted model was 0.594 (CI 0.577–0.610). The adjusted model had higher AUC (0.673, CI 0.657–.690]; P

Oral complications of cancer therapy are common, markedly symptomatic, negatively impact patients' quality of life, and add significantly to the cost of care. Patients' risk of treatment-related toxicities is not uniform; most patients suffer at least one side effect, while others tolerate treatment without any. Understanding those factors which impact risk provides opportunities to customize cancer treatment plans to optimize tumor kill and minimize regimen-related toxicities. Oral mucositis (OM) is an iconic example of a clinically significant and common complication of head and neck radiotherapy. Individuals' OM risk is governed by the cumulative impact of factors related to treatment, the tumor, and the patient. In addition to OM risk prediction, a second opportunity to apply precision medicine will evolve as viable treatment options become available. Patients vary widely in how well or poorly they respond to specific treatments. What works well in one individual, might fail in another. Prospective determination of the likelihood of a patient's response or non-response is based on a range of biological interactions. Coupled with risk determination, the application of precision medicine will allow caregivers, patients, and payers to integrate risk/benefit to optimize the probability that the best treatment is be given to the most appropriate patients.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of antineoplastic therapy that restore anti-tumor immunity. Consequences of this enhanced immune response include a multitude of immune related adverse events (irAEs) that can affect any body system, including the mouth. Orofacial irAEs reproduce features of numerous immune-mediated conditions, including oral lichen planus, mucous membrane pemphigoid, and Sjögren syndrome, among others. The aim of this review is to summarize known orofacial irAEs and to familiarize oral healthcare providers with how to identify and manage these toxicities as part of the care team for patients treated with ICIs.

Objective To explore the causes and levels of moral distress experienced by clinicians caring for the low-income patients of safety net practices in the USA during the COVID-19 pandemic.Design Cross-sectional survey in late 2020, employing quantitative and qualitative analyses.Setting Safety net practices in 20 US states.Participants 2073 survey respondents (45.8% response rate) in primary care, dental and behavioural health disciplines working in safety net practices and participating in state and national education loan repayment programmes.Measures Ordinally scaled degree of moral distress experienced during the pandemic, and open-ended response descriptions of issues that caused most moral distress.Results Weighted to reflect all surveyed clinicians, 28.4% reported no moral distress related to work during the pandemic, 44.8% reported ‘mild’ or ‘uncomfortable’ levels and 26.8% characterised their moral distress as ‘distressing’, ‘intense’ or ‘worst possible’. The most frequently described types of morally distressing issues encountered were patients not being able to receive the best or needed care, and patients and staff risking infection in the office. Abuse of clinic staff, suffering of patients, suffering of staff and inequities for patients were also morally distressing, as were politics, inequities and injustices within the community. Clinicians who reported instances of inequities for patients and communities and the abuse of staff were more likely to report higher levels of moral distress.Conclusions During the pandemic’s first 9 months, moral distress was common among these clinicians working in US safety net practices. But for only one-quarter was this significantly distressing. As reported for hospital-based clinicians during the pandemic, this study’s clinicians in safety net practices were often morally distressed by being unable to provide optimal care to patients. New to the literature is clinicians’ moral distress from witnessing inequities and other injustices for their patients and communities.

DisclaimerThis article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols.ObjectiveThis position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT).BackgroundThere is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients’ quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care.MethodsA literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed.ResultsThere is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors.ConclusionsThere is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.