Evidence-based Treatment Recommendations Research Articles

The Pathophysiology and Management of Pathologic Scarring-a Contemporary Review.

Significance: Pathologic scarring occurs secondary to imbalances in the cellular mechanisms of wound healing and affects millions of people annually. This review article aims to provide a concise overview of the pathophysiology and management of pathologic scarring for clinicians and scientists alike. Recent Advances: Contemporary research in the field has identified aberrations in transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) signaling pathways as key drivers of pathologic scar formation; indeed, this pathway is targeted by many treatment modalities and translational investigations currently underway. Although intralesional injection of corticosteroids has been the gold standard in the treatment of pathologic scarring, studies show greater treatment efficacy with the use of combination injections such as triamcinolone/5-fluorouracil and triamcinolone/botulinum toxin. Adjunctive therapies including ablative fractional carbon dioxide/erbium-doped yttrium aluminum garnet and non-ablative pulsed-dye lasers, microneedling, and carboxytherapy have shown encouraging results in small cohort studies. Translational investigations involving the use of nanogels, RNA interference, and small molecules targeting TGF-β/SMAD pathways are also currently underway and hold promise for the future. Critical Issues: The heterogeneous nature of hypertrophic scars and keloids poses significant challenges in formulating standardized treatment and assessment protocols, thereby limiting the conclusions that can be drawn. Future Directions: Rigorous clinical trials into the individual and synergistic effects of these therapies would be ideal before any definitive conclusions or evidence-based treatment recommendations can be made. Owing to the heterogeneity of the pathology and patient population, well-conducted cohort studies may be the next best option.

Expert consensus on vestibular rehabilitation in vestibular disorders

Vestibular rehabilitation therapy (VRT) is a highly effective treatment approach for addressing both peripheral and central vestibular disorders, offering the ability to significantly improve patients' coordination and control across the vestibular, visual, and proprioceptive systems, all of which are crucial factors in maintaining balance. By promoting vestibular compensation, VRT has been shown to mitigate or even eliminate symptoms of dizziness, vertigo, and instability. With the rapid development of vestibular research, VRT has evolved into a more individualized and precise treatment approach based on evidence-based medicine. Its clinical effectiveness has been increasingly validated in numerous studies. With the involvement of multidisciplinary experts, this article aims to reach a consensus on the pre-treatment evaluation, formulation/implementation of treatment plans, and evidence-based treatment recommendations for common vestibular disorders, focusing on the prospects of vestibular rehabilitation. The goal is to further standardize and update VRT protocols for different vestibular disorders, providing comprehensive and context-specific guidance primarily tailored to the Chinese healthcare landscape, with a notable emphasis on its clinical applicability. Concurrently, it aspires to present new insights and serve as a valuable reference point for forthcoming high-quality clinical research on vestibular rehabilitation in China.

Autologous platelet concentrates in regenerative dentistry - A narrative literature review. Part I: Theoretical and legal aspects of the PR(G)F application

The use of autologous platelet concentrates (APC) such as platelet-rich fibrin (PRF) and/or plasma rich in growth factors (PRGF®) is considered an established treatment modality in re-generative dentistry. The possibility of delivering growth factors over aclinically relevant time of several days seems particularly interesting in the context of wound healing.The growing body of evidence in the field of APC requires a continuous and actual knowledge of the literature for being able to make evidence-based treatment recommendations with a realistic assessment of possible advantages of this technology.PR(G)F can be applied in solid or liquid form, pure or in combination with other biomaterials. Both appear to be reasonable, depending on the clinical indication and/or desired treatment outcomes. Because of the many different factors that can affect the PR(G)F products final characteristics, a basic understanding of these parameters is desirable for choosing the most suitable product and/or optimizing its clinical application. This review aims to provide an over-view of relevant theoretical, practical, legal and biologic aspects of APCs.

Obesity and Aging: Optimizing Health at the Intersection of Ageism and Weight Bias

Obesity is a chronic and complex disease that can negatively impact health, functioning and quality of life. In the past decade, obesity's largest prevalence growth occurred in older adults, particularly among racial and ethnic minorities. By the year 2030, an estimated 50% of the population over 65 is likely to be living with obesity. Until recently, little attention has been given to obesity as a chronic disease, and those living with obesity have encountered challenges accessing high quality medical care. Despite growing evidence for bariatric and obesity medicine, these treatments remain inaccessible for most patients, especially for older adults. Obesity research focused on older adults has been very limited and ideal weight standards for older adults are more controversial, especially in later life where frailty and sarcopenia may develop. As concerns about the public health effects of obesity have risen in the U.S., so too have negative and stigmatized views of individuals with obesity. Weight stigma has serious negative emotional and physical health consequences including low self-esteem, negative body image, engagement in disordered eating patterns, reduced physical activity and may promote weight gain. Older adults with obesity may encounter the double stigma of both ageism and weight bias, which are two of the most socially acceptable forms of bias and discrimination in the U.S. This interactive session will focus on three areas related to obesity and older adults. Through case examples, small and large group discussions, the presenters will: i) explore potential weight bias amongst participants and discuss strategies to mitigate this bias in working with older adults; ii) discuss complex connections between obesity and frailty syndrome in older adults, and the risks associated with weight loss in later life; iii) introduce evidence-based assessment and treatment recommendations for older adults interested in obesity treatment. This session will focus on the role of psychiatrists and other mental health clinicians in the care of older patients with co-morbid obesity and mental health disorders. Also, presenters will discuss the importance of increasing awareness, advocacy, and practical strategies to combat the impact of weight bias and ageism in healthcare settings. Ultimately, the goal is to raise awareness of this complex problem and provide clinically helpful information to improve care for older patients with obesity. This symposium is sponsored by the AAGP's IDEA committee.

A Dutch paediatric palliative care guideline: a systematic review and evidence-based recommendations for symptom treatment

BackgroundChildren with life-threatening and life-limiting conditions can experience high levels of suffering due to multiple distressing symptoms that result in poor quality of life and increase risk of long-term distress in their family members. High quality symptom treatment is needed for all these children and their families, even more so at the end-of-life. In this paper, we provide evidence-based recommendations for symptom treatment in paediatric palliative patients to optimize care.MethodsA multidisciplinary panel of 56 experts in paediatric palliative care and nine (bereaved) parents was established to develop recommendations on symptom treatment in paediatric palliative care including anxiety and depression, delirium, dyspnoea, haematological symptoms, coughing, skin complaints, nausea and vomiting, neurological symptoms, pain, death rattle, fatigue, paediatric palliative sedation and forgoing hydration and nutrition. Recommendations were based on evidence from a systematic literature search, additional literature sources (such as guidelines), clinical expertise, and patient and family values. We used the GRADE methodology for appraisal of evidence. Parents were included in the guideline panel to ensure the representation of patient and family values.ResultsWe included a total of 18 studies that reported on the effects of specific (non) pharmacological interventions to treat symptoms in paediatric palliative care. A few of these interventions showed significant improvement in symptom relief. This evidence could only (partly) answer eight out of 27 clinical questions. We included 29 guidelines and two textbooks as additional literature to deal with lack of evidence. In total, we formulated 221 recommendations on symptom treatment in paediatric palliative care based on evidence, additional literature, clinical expertise, and patient and family values.ConclusionEven though available evidence on symptom-related paediatric palliative care interventions has increased, there still is a paucity of evidence in paediatric palliative care. We urge for international multidisciplinary multi-institutional collaboration to perform high-quality research and contribute to the optimization of symptom relief in palliative care for all children worldwide.

Abstract IA008: Racial disparities in guideline-concordant endometrial cancer treatment

Abstract Mortality associated with endometrial cancer is 98% higher among Black as compared with White women. A large body of literature has evaluated differential treatment patterns as a potential determinant of increased mortality among Black women. In most studies, receipt of individual endometrial cancer treatment components (i.e., surgery, radiation, chemotherapy) is compared between Black and White women. Moreover, individual treatment components are typically considered binary variables (received vs. not received) with the received category reflecting a wide spectrum of treatments received. For example, women who receive one vs. six cycles of chemotherapy would be similarly labeled as receiving chemotherapy, despite a clear difference in treatment intensity. In contrast, recent studies have begun to evaluate racial and ethnic differences in the complete course of treatment as a unit, within the context of established guidelines. The National Comprehensive Cancer Network guidelines provide evidence-based endometrial cancer treatment recommendations based on clinical trials and observational research. Surgery is the first step of guideline-concordant treatment and pathology factors captured from surgery inform adjuvant treatment recommendations. Since the distribution of tumor characteristics that guide treatment recommendations varies between Black and White women, we should expect racial differences in use of adjuvant radiation and chemotherapy. However, when conceptualizing treatment as guideline-concordant vs. discordant, racial and ethnic differences clearly signal disparate quality of care. In this presentation, we will discuss the need for research on endometrial cancer treatment disparities to shift from a paradigm of exploring individual treatment components to one in which receipt of guideline-concordant treatment is the focus. Moreover, through the lens of a recently funded grant, we will discuss the value of using an explicit disparities definition in analyses of guideline-concordant treatment, which allows for decomposition of the sources of racial and ethnic disparities. Differences in healthcare related to clinical need or preference are not considered sources of disparities, reflecting the normative view that these differences are acceptable, and therefore, just. On the other hand, unjust sources of disparities include the operation of healthcare systems, the legal and regulatory climate, and discrimination, among other factors. In addition to the selection of a rigorous and nuanced disparities definition, future research on guideline-concordant treatment disparities should investigate the role of multilevel factors that reflect the social determinants of health. Cancer health disparities are entrenched in the social determinants of health, which cannot be effectively addressed at the individual-level alone. Citation Format: Ashley S. Felix. Racial disparities in guideline-concordant endometrial cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA008.

WHO Guidelines about Mental Health Gap Action Programme (mhGAP) for mental, neurological and substance use disorders: Review and Comments

Introduction: The World Health Organization (WHO) has been instrumental in developing evidence-based guidelines to address mental, neurological, and substance use disorders through its Mental Health Gap Action Programme (mhGAP). These guidelines provide essential recommendations for healthcare professionals to deliver effective care in non-specialized health settings. Aim: This article aims to review and analyze the updated WHO guidelines on the mhGAP intervention for mental, neurological, and substance use disorders, focusing on their significance, content, and implications for clinical practice. Methods: A comprehensive review of the WHO documents published in 2023, including the "mhGAP intervention guide for mental, neurological, and substance use disorders in non-specialized health settings" and the "Update of the Mental Health Gap Action Programme (mhGAP) guidelines for mental, neurological, and substance use disorders, 2015," was conducted. The review examines the scope of the guidelines, their recommendations, and the evidence supporting them. Results: The updated WHO guidelines cover a wide range of mental health conditions, including alcohol use disorders, anxiety disorders, depression, and more. Each guideline provides evidence-based recommendations for prevention, diagnosis, and treatment, with the aim of improving access to quality mental health care in diverse healthcare settings. The guidelines are freely accessible online through the WHO's mhGAP Evidence Resource Centre website, offering detailed evidence profiles and recommendations for healthcare professionals. Conclusions: The WHO guidelines on the mhGAP represent a critical resource for healthcare professionals worldwide, offering evidence-based guidance for the delivery of mental health care. By providing standardized recommendations informed by the best available evidence, these guidelines support the implementation of evidence-based practice and contribute to improved patient outcomes. The WHO's commitment to updating and disseminating these guidelines underscores its dedication to promoting mental health equity and advancing evidence-based care globally.

Virtual first: implementation of a novel sleep telehealth platform in the United States military

BackgroundThere is a gross shortage of sleep specialist providers within the military health system. Telehealth and mobile health represent promising approaches to increase access to high quality, cost-effective care in the U.S military.ObjectivesThis paper reports findings from a mixed-methods clinical implementation study of a novel sleep telehealth platform at two military treatment facilities in the National Capitol Region. The platform includes a mobile app and integrated wearable sensors (i.e., a commercial off-the-shelf sleep tracker [Fitbit]). The primary purpose was to evaluate the implementation of a 10-day remote monitoring assessment and provision of evidence-based sleep treatment recommendations to patients and providers. In addition, we sought to observe, in an exploratory manner, subsequent engagement with the app during 5 days of personalized sleep education and training.MethodsPatients with sleep problems completed an intensive 10-day remote monitoring assessment that included a baseline intake questionnaire, daily sleep diaries, twice daily symptom surveys, and Fitbit. Based on this assessment, patients received personalized assessment results. Concurrently, a provider report was generated that included provisional diagnoses and evidence-based treatment recommendations. Next, participants gained access to personalized sleep education and trainings within the mobile app. Within an established implementation science framework, outcomes were assessed via behavioral adherence (engagement with the app) and separate questionnaires for patients and providers. Last, we conducted four focus groups with patients and 12 key informant interviews with primary care managers (PCMs) and economic stakeholders to seek feedback and recommendations for future directions.ResultsTwo hundred and seventy patients participated in the study. Using validated research questionnaires, participants reported high-risk for obstructive sleep apnea (65.6%), moderate to severe insomnia (38.2%), and moderate to severe daytime sleepiness (38.5%), and moderate to severe anxiety (14.1%) and depressive (20.4%) symptoms. Total sleep time was 6.6 (SD = 1.8) h based on sleep diaries and 6.1 (SD = 1.8) h based on Fitbit. Regarding implementation, reach, effectiveness, adoption, implementation, and maintenance were all notably high, based on quantitative and qualitative data from participants and PCMs.ConclusionsSleep telehealth and mobile health represent promising approaches to increase access to cost-effective, evidence-based care for sleep disorders in the U.S. military.

Immune checkpoint inhibitors for patients with microsatellite instability-high colorectal cancer: protocol of a pooled analysis of clinical trials.

Colorectal cancer (CRC) is the third most common cause of cancer and the second leading cause of cancer-related deaths worldwide. Microsatellite instability-high (MSI-H) is a distinct molecular subtype of CRC that occurs in approximately 15% of all cases. Recently, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic approach for patients with MSI-H colorectal cancer, exhibiting higher response rates than standard chemotherapies. To assess the effectiveness and safety of ICIs for the treatment of patients with MSI-H CRC, we propose a comprehensive pooled analysis of clinical trial data. A systematic search of multiple electronic databases, including PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov, will be conducted from their inception until September, 2023 to identify eligible randomized controlled trials (RCTs) and non-randomized studies. Inclusion criteria comprise studies of adult patients with histologically confirmed MSI-H CRC treated with immune checkpoint inhibitors, with a comparison to a control group receiving conventional therapies. Outcomes of interest will be overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse events (AEs). The Cochrane Risk of Bias tool and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool will be employed to evaluate the methodological quality of included studies. A random-effects model using the DerSimonian and Laird method will be applied for pooling the effect estimates, calculating hazard ratios (HRs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Heterogeneity will be assessed using I² statistics, and subgroup analysis and meta-regression will be performed to explore potential effect modifiers in case of substantial heterogeneity. Publication bias will be evaluated with funnel plots and Egger's test. Sensitivity analysis will be conducted to assess the robustness of the results. This meta-analysis will synthesize available evidence from clinical trials on immune checkpoint inhibitors in treating MSI-H colorectal cancer. The findings will offer valuable information about the effectiveness and safety of ICIs in this patient population, contributing to the refinement of clinical guidelines and enhancing the decision-making process for healthcare providers, policy-makers, and patients. The comprehensive analysis of subgroups and sensitivity allows for an in-depth understanding of potential effect modification, providing essential directions for future research. This study will involve the use of published data; hence, ethical approval is not required. The results of the study will be disseminated through publications in peer-reviewed journals and presentations at relevant conferences. The findings will potentially impact clinical decision-making and contribute to the development of evidence-based treatment recommendations for patients with MSI-H colorectal cancer. Open Science Framework identifier, 10.17605/OSF.IO/ZHJ85.

Influence of cancer in pregnancy on obstetric and neonatal outcomes: an observational retrospective cohort study.

The study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management. We conducted an observational retrospective cohort study among pregnant patients with cancer in 7 Chinese tertiary A hospitals from 2003 to 2021. We conducted multiple logistic regression to determine the influence of various factors on preterm birth and small-for-gestational-age infants, log-binomial regression to analyze temporal changes, and χ² tests to explore the effects of cancer type/treatment. Of 204 women, 17% terminated their pregnancies; 59% received pre-delivery treatment. Every 6 years, the rates of pregnancy termination (relative risk [RR]=0.48; 95% confidence interval [CI]=0.35-0.67) and iatrogenic preterm births (RR=0.73; 95% CI=0.54-0.98) reduced, and that of pre-delivery treatment increased, mainly due to increased rates of surgery (RR=1.87; 95% CI=1.31-2.67). Maternal systemic diseases were related to small-for-gestational-age infants (odds ratio [OR]=12.02; 95% CI=1.82-79.43). Chemotherapy with taxanes plus platinum-based agents was related to adverse obstetric outcomes (OR=1.87; 95% CI=1.42-2.46; p<0.05). Thyroid (OR=0.36; 95% CI=0.22-0.57) and ovarian cancer (OR=0.70; 95% CI=0.50-0.98) were associated with fewer cesarean sections. Thyroid cancer was associated with fetal growth restriction (OR=5.21; 95% CI=1.21-22.55). Rates of pregnancy termination in cancer declined. Taxane plus platinum-based chemotherapy was associated with adverse obstetric outcomes. Cancer type influenced outcomes. Chinese Clinical Trial Register Identifier: ChiCTR2100044292.

Understanding Medication Nonadherence in Crohn's Disease Patients: A Qualitative Evaluation.

Immune-modifying medications are widely available and recognized as valuable by most gastroenterologists. However, approximately 40% of patients with Crohn's disease (CD) do not comply with regimens using these medications, resulting in complications, hospitalization, and surgeries. We sought to identify factors that motivate adherence or nonadherence with medication recommendations for CD. We conducted qualitative interviews with patients living with CD who were identified as adherent or nonadherent to immune-modifying medication recommendations by their treating gastroenterologist. Semistructured interview guides were developed based on an established framework for understanding health behaviors. We conducted content analysis of the resulting qualitative data using an inductive-deductive approach to identify emergent themes that influence medication decision-making. Twenty-five patients with CD completed interviews for this study. Interviews were independently coded and analyzed for thematic content. Two broad domains emerged comprising (1) themes reflected in the Theoretical Domains Framework and (2) novel themes specific to medication decision-making in CD. Adherent patients conveyed a sense of trust in science and healthcare provider expertise, while nonadherent patients were more likely to express beliefs in their ability to self-manage CD, concern about risks associated with medication, and a general ambivalence to treatment. There are clear cognitive, behavioral, and relational factors that guide patients' medication-related decision-making. Several of the factors share features of other behavioral change and decision-making processes, while others are specific to the experience of patients with CD. A fuller understanding of these factors is essential to developing effective behavioral interventions to improve adherence to evidence-based treatment recommendations.

The impact of ulinastatin on wound infection and healing in patients with burn wounds: A meta-analysis.

Burn injuries result in localised tissue damage and precipitate systemic responses; routine clinical treatments, which typically include metabolic nutritional support and anti-infection therapies, do not yield optimal outcomes. Therefore, we aimed to systematically evaluate the effects of ulinastatin on wound infection and healing in patients with burns to provide reliable evidence-based recommendations for burn treatment. An electronic search of the Web of Science, PubMed, Cochrane Library, Embase, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, supplemented by manual searches, was conducted from database inception to October 2023 to collect randomised controlled trials (RCTs) assessing the efficacy of ulinastatin for the treatment of burns. Two researchers screened all retrieved articles according to the inclusion and exclusion criteria; the included studies were evaluated for quality, and the relevant data were extracted. Stata 17.0 software was employed for data analysis. Overall, 8 RCTs with 803 patients were included, with 404 and 399 in the ulinastatin and conventional treatment groups, respectively. The analysis revealed that wound infections (odds ratio [OR] = 0.08, 95% CI: 0.02-0.35, p = 0.001) and complications (OR = 0.21, 95% CI: 0.10-0.42, p < 0.001) were significantly lower, and wound healing time (standardised mean differences [SMD] = -1.31, 95% CI: -2.05 to -0.57, p = 0.001) was significantly shorter, in the ulinastatin groups than in the control group. This meta-analysis revealed that ulinastatin can effectively reduce the incidence of wound infections and complications and significantly shorten the duration of wound healing in patients with burns, thereby promoting early recovery in these patients.

Utilisation of radiotherapy in lung cancer: A scoping narrative literature review with a focus on the introduction of evidence-based therapeutic approaches in Europe

Background and purposeThe aim of this study was to review the published studies on the utilisation of radiotherapy in lung cancer (both small and non-small cell lung cancer, SCLC and NSCLC) patients in European countries with a population-based perspective. Material and methodsA literature search since January 2000 until December 2022 was carried out. Only English-published papers were included, and only European data was considered. PRISMA guidelines were followed. A scoping narrative review was undertaken due to the hetereogeneity of the published papers. Results38 papers were included in the analysis, with the majority from the Netherlands (52.6%) and the UK (18.4%). Large variability is observed in the reported radiotherapy utilisation, around 40% for NSCLC in general and between 26 and 42% in stage I NSCLC. Stereotactic body radiotherapy (SBRT) shows a wide range of utilisation across countries and over time, from 8 to 63%. Similary, in stage III lung cancer, chemoradiotherapy (CRT) utilisation varied considerably (11–70%). Eleven studies compared radiotherapy utilisation between older and younger age-groups, showing that younger patients receive more CRT, while the opposite applies for SBRT. An widespreadlack of data on relevant covariates such as comorbidty and health-services related variables is observed. ConclusionThe actual utilisation of radiotherapy for lung cancer reported in patterns-of-care studies (POCs) is notably lower than the evidence-based optimal utilisation. Important variability is observed by country, time period, stage at diagnosis and age. A wider use of POCs should be promoted to improve our knowledge on the actual application of evidence-based treatment recommendations.

Musculoskeletal and Psychological Rehabilitation.

Although it has long been believed that stress has a detrimental effect on health and the risk of disease, little research has been done on the precise mechanisms by which this happens. The literature produced by past workers suggests many possibly intersecting mechanistic pathways that might be useful for future fundamental and clinical study. Exercise has been thoroughly researched as a non-pharmacologic strategy to increase bone mass. Many evidence-based treatment recommendations for patients suffering from osteoporosis-related fractures, potential courses of care, and rehabilitation concur that multidisciplinary therapy would be the most beneficial. Older and recent articles about musculoskeletal and psychological rehabilitation in the management of osteoporosis published in prominent and reputed journals are reviewed. Important and interesting information from some of the cross-references is also included. Opinions and impressions from the experience of treating osteoporosis are added while describing various aspects of psychological and physical rehabilitation. The recent evidence, reviewed here, also indicates the possibility of cross-effects between osteoporosis and psychological issues. A multi-factorial and personalised strategy should be explored for improved outcomes in patients under psychological stress, particularly those at increased risk of osteoporosis development. Reviewing current publications, the objectives of rehabilitation are evolving based on the disease's stage. For example, during the initial stage of a vertebral body collapse, the patient is treated with bracing, physical therapy, education, local and systemic analgesics, and a brief period of bed rest. The need to mobilise the patient carefully and safely along with a mix of medical care, dietary supplements, rehabilitation, and instructions to facilitate daily living activities, are endorsed to manage post-fracture osteoporosis. This chapter is not to make treatment advice, but rather to outline potential connections between psychological stress and low bone density and to emphasise potential multi-system consequences of pharmaceutical therapies. The goal is to enhance activities of daily living, which will increase safety, minimise falls, and maintain bone mass. Osteoporosis and fragility fractures can be prevented and managed with regular medical check-ups, daily exercise and yoga, a healthy diet, fall prevention measures,recreational groupactivities, supportive medications, control ofcomorbidities, use of assistivedevices, and customised rehabilitation programmes.

Evidence-Based Recommendations for Induction Treatment of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients; A Scoping Review

Introduction Multiple myeloma is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells within the bone marrow, with an increasing incidence and mortality in the last decade. Eligibility for stem cell transplantation plays a crucial role in determining the approach to treatment, with transplant eligible patients undergoing triple induction therapy with an immunomodulatory agent, a proteasome inhibitor, and steroid. We aimed to review the recent data on the available treatment options for newly diagnosed multiple myeloma (NDMM) in transplant eligible patients. Methods A scoping review was conducted according to the PRISMA 2020 guidelines utilizing the PubMed and Embase databases. The inclusion criteria was phase II or III clinical trials pertaining to the use of triple and quadruple therapy in NDMM patients, from the year 2010 onwards. A total of 2377 search results were screened, with 510 undergoing full-text screening against the inclusion criteria. Covidence was used to facilitate the screening process (Figure 1). Results Forty studies were included in the analysis. Eleven trials were based on Daratumumab induction. Additionally, two trials each utilized Isatuximab and Carfilzomib-based induction. One trial employed induction therapy containing Elotuzumab, and another utilized Cyclophosphamide. Addition of Daratumumab to the triplet regimen resulted in significant improvements in response rates and depth of responses. CASSIOPEIA trial demonstrated a notable improvement in minimal residual disease (MRD), with VTd treatment yielding 44% MRD, while Dara-VTd regimens achieved 64% MRD. Similarly, complete response (CR) rates increased from 26% to 39%, respectively. GRIFFIN trial revealed a remarkable 55% reduction in the risk of disease progression for patients with Dara-RVd . Moreover, the estimated 48-month progression-free survival (PFS) rate was 87.2% in the Dara-RVd group, compared to 70% in the RVd group. Notably, the median PFS was not reached in either treatment arm. The Lyra trial, which analyzed Dara-CyBorD followed by Dara maintenance, demonstrated a CR rate of 48.7% for transplant patients and 29.8% for non-transplant patients, respectively. Additionally, the MASTER trial revealed that Dara-KRd/autologous hematopoietic cell transplant (AHCT) led to a high rate of MRD negativity, with 80% of patients achieving MRD negativity. The two-year PFS was 87%. Furthermore, the addition of Isatuximab and Carfilzomib to the treatment regimen demonstrated favorable outcomes in terms of MRD and PFS (Table 1). The addition of Elotuzumab did not lead to a significant improvement in outcomes. Moreover, caution is warranted when using Cyclophosphamide, given its less favorable safety profile and limited additional benefit in survival outcomes (MRD: 27% in +Cyclophosphamide arm vs. 35% without), including a temporary decline in health-related quality of life. Conclusion In conclusion, this scoping review underscores the significance of individualized treatment approaches for multiple myeloma based on clinical trial results. Each induction regimen has shown varying levels of efficacy and safety, offering clinicians flexibility to tailor treatments for different patient populations. The results from these trials will serve as valuable benchmarks and inform future research in the quest for improved therapies for NDMM patients.

Clinical Practice Gaps in Managing Patients with Myelofibrosis: Comparison of Healthcare Professional and Expert Treatment Choices Provided to an Online Decision Support Tool

Background: Myelofibrosis (MF) is a rare hematologic malignancy for which treatment has evolved considerably in recent years, with 3 JAK inhibitors now approved in the United States to manage this disease. With numerous therapeutics in phase III trials, the complexity of treatment selection is likely to increase in the coming years. To assist hematology/oncology healthcare professionals (HCPs), we developed an online decision support tool designed to provide case-specific treatment recommendations from 5 MF experts. Here, we report an analysis of cases entered into the tool by HCPs, comparing their planned treatment with expert recommendations to determine differences in clinical practice and areas of educational need. Methods: In February 2023, 5 MF experts provided evidence-based treatment recommendations for 45 distinct MF case scenarios that were defined by multiple key factors, including the presence of MF symptoms, splenomegaly, or anemia; platelet count; prognostic risk group; and previous JAK inhibitor therapy. To use the tool, HCPs entered their patients' characteristics and their intended treatment plan; recommendations from each of the 5 experts based on those same characteristics were then provided. In this analysis, the intended treatment plans of HCPs were compared with expert recommendations to determine areas of discordance and agreement. Results: In May/June 2023, 91 cases were entered into the tool (84% of cases by physicians); 72% of respondents reported treating 1-4 patients with MF per month (n = 32), and 61% sought recommendations for a specific patient in their practice (n = 28). A lack of concordance between HCP and expert treatment choices was observed for many case scenarios (Table). For example, for case patients with lower prognostic risk and MF signs/symptoms, experts most frequently recommended ruxolitinib (85%) in contrast to HCPs, who recommended ruxolitinib for 38% of these cases. Similarly, discordance was noted for several case scenarios of patients with higher-risk MF who were not suitable for transplant and required a treatment change following initial therapy with ruxolitinib. Of note, subtle variance was observed among experts for specific second-line case scenarios, including when to add on to current therapy vs switching to a new JAK inhibitor, which may reflect the burgeoning area of clinical practice in defining JAK inhibitor failure and determining subsequent second-line treatment paradigms with several JAK inhibitors now available. Of the 23 HCP cases seeking recommendations for patients with higher prognostic risk, 74% sought recommendations in the post-ruxolitinib setting. Overall, after reviewing expert recommendations, 81% of HCP respondents indicated that they would change their treatment approach or that the recommendations confirmed their treatment strategy (n = 32). Conclusions: Analysis of data from an online decision support tool indicates differences among experts and HCPs in contemporary management of patients with MF, and data suggest that a decision support tool can affect HCP treatment decisions in a rapidly evolving therapeutic landscape, potentially improving patient care. In-depth analyses with additional HCP cases will be presented.

Patient Engagement and Provider Effectiveness of a Novel Sleep Telehealth Platform and Remote Monitoring Assessment in the US Military: Pilot Study Providing Evidence-Based Sleep Treatment Recommendations.

Sleep problems are common and costly in the US military. Yet, within the military health system, there is a gross shortage of trained specialist providers to address sleep problems. As a result, demand for sleep medicine care far exceeds the available supply. Telehealth including telemedicine, mobile health, and wearables represents promising approaches to increase access to high-quality and cost-effective care. The purpose of this study was to evaluate patient engagement and provider perceived effectiveness of a novel sleep telehealth platform and remote monitoring assessment in the US military. The platform includes a desktop web portal, native mobile app, and integrated wearable sensors (ie, a commercial off-the-shelf sleep tracker [Fitbit]). The goal of the remote monitoring assessment was to provide evidence-based sleep treatment recommendations to patients and providers. Patients with sleep problems were recruited from the Internal Medicine clinic at Walter Reed National Military Medical Center. Patients completed intensive remote monitoring assessments over 10 days (including a baseline intake questionnaire, daily sleep diaries, and 2 daily symptom surveys), and wore a Fitbit sleep tracker. Following the remote monitoring period, patients received assessment results and personalized sleep education in the mobile app. In parallel, providers received a provisional patient assessment report in an editable electronic document format. Patient engagement was assessed via behavioral adherence metrics that were determined a priori. Patients also completed a brief survey regarding ease of completion. Provider effectiveness was assessed via an anonymous survey. In total, 35 patients with sleep problems participated in the study. There were no dropouts. Results indicated a high level of engagement with the sleep telehealth platform, with all participants having completed the baseline remote assessment, reviewed their personalized sleep assessment report, and completed the satisfaction survey. Patients completed 95.1% of sleep diaries and 95.3% of symptom surveys over 10 days. Patients reported high levels of satisfaction with most aspects of the remote monitoring assessment. In total, 24 primary care providers also participated and completed the anonymous survey. The results indicate high levels of perceived effectiveness and identified important potential benefits from adopting a sleep telehealth approach throughout the US military health care system. Military patients with sleep problems and military primary care providers demonstrated high levels of engagement and satisfaction with a novel sleep telehealth platform and remote monitoring assessment. Sleep telehealth approaches represent a potential pathway to increase access to evidence-based sleep medicine care in the US military. Further evaluation is warranted.

Primary Biliary Cholangitis (PBC)-Autoimmune Hepatitis (AIH) Variant Syndrome: Clinical Features, Response to Therapy and Long-Term Outcome.

Standardization of diagnostic criteria of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) variant syndrome (AIH-PBC VS) has not been achieved so far and evidence-based recommendations for monitoring and treatment of the disease are still lacking. Our study aimed to assess the prevalence, biochemical, and serological features, as well as the clinical course, of VS. We performed a retrospective study including all patients with VS between 1999 and 2020 in four German centers. Data on demographic parameters, biochemical and serological tests, treatment, and outcome were collected. Of 90 patients (3.1%) meeting Paris criteria for VS diagnosis, 65.6% showed AIH and PBC histological features, while biochemical Paris criteria were observed comparatively rarely. Further antibodies, which were not part of the diagnostic criteria of VS, were found in a subgroup of patients with available data (ACA: 30.0%; anti-CENP-A: 25.0%; anti-CENP-B: 33.3%; anti-SP100: 21.4%). Biochemical response was more frequently observed in patients treated with a combined therapy of ursodeoxycholic acid (UDCA) and immunosuppression (IS). Liver cirrhosis was detected in 31 patients (34.4%) and 25 patients (27.8%) developed clinical manifestations of portal hypertension. Biochemical Paris criteria of VS were rarely detected, thus implying that these cut-off values should be redefined. Regarding pharmacological treatment, combined therapy of UDCA and IS appeared to be more effective than monotherapy with UDCA.

CNSC-04. DIAGNOSIS AND TREATMENT OF PERIPHERAL AND CRANIAL NERVE TUMORS WITH EXPERT RECOMMENDATIONS: AN EUROPEAN NETWORK FOR RARE CANCERS (EURACAN) INITIATIVE

Abstract BACKGROUND The 2021 WHO classification of the CNS Tumors identifies as “Peripheral nerve sheath tumors” (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. Material and methods. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. RESULTS Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively. CONCLUSIONS Given the heterogeneity and rarity of these tumors, there is a paucity of well-powered clinical trials, thus it is not possible to generate evidence-based treatment recommendations for non-surgical modalities. However, some clinical trials have been reported on targeted therapies in plexiform neurofibromas of NF1 patients or in heterogenous cohorts of soft-tissue tumors, including MPNSTs, with initial data of efficacy that need to be further investigated.

Abstract 14354: The Impact of Riociguat in Pulmonary Arterial Hypertension Patients With Comorbidities Included in Interventional Clinical Trials

Background: The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing, however, there are few published data from these patients in PAH therapy clinical trials meaning that evidence-based treatment recommendations have not been made. Aim: This post-hoc analysis of pooled riociguat clinical trial data assessed the impact of riociguat in patients with PAH and comorbidities. Methods: All interventional studies of riociguat in patients with PAH (PATENT-1, PATENT PLUS, RESPITE, MOTION, REPLACE, and the Phase II study) were included in the pooled analysis. The safety of riociguat and placebo was assessed in patients with ≥3 comorbidities vs &lt;3 comorbidities. Safety was assessed by adverse events (AEs) and serious AEs (SAEs). Comorbidities included: age ≥65 years, body mass index ≥30 kg/m 2 , history of essential hypertension, diabetes mellitus, history of significant coronary artery disease, and atrial fibrillation. Results: The 609 patients who received riociguat and 132 patients who received placebo in the main phase clinical trials of riociguat were included in the analysis. Of these, 113 patients (19%) in the riociguat group and 21 patients (16%) in the placebo group had ≥3 comorbidities. In both treatment groups, AE rates were higher in patients with ≥3 comorbidities vs &lt;3 comorbidities (riociguat 93% vs 86%; placebo 95% vs 84%); with most AEs being mild or moderate. Study drug-related AE rates were similar in both treatment groups and in patients with ≥3 comorbidities vs &lt;3 comorbidities (riociguat 54% vs 56%; placebo 52% vs 52%). SAE rates were higher in riociguat-treated patients with ≥3 comorbidities vs &lt;3 comorbidities (25% vs 12%); of these, 4% and 3% were study drug-related, respectively. In patients with ≥3 comorbidities, study drug-related SAE rates were higher in those receiving placebo vs riociguat (10% vs 4%). AE rates leading to study drug discontinuation were higher in patients with ≥3 comorbidities vs &lt;3 comorbidities (riociguat 6% vs 4%; placebo 10% vs 6%), whereas AE rates leading to death were similar in both groups (riociguat 2% vs 1%; placebo 0% vs 4%). Conclusion: These data suggest that riociguat had an acceptable tolerability profile in PAH patients with comorbidities with most AEs being mild or moderate.