Development of a Uniform Apheresis Case Report Form for Standardized Collection of Apheresis Data.

Apheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form.

Delphi expert consensus for whole slide imaging in thyroid cytopathology.

OBJECTIVE: Despite an increase in thyroid fine needle aspiration (FNA) and advances in whole slide imaging (WSI) adoption, digital pathology is still considered inadequate for primary diagnosis of these cases. Herein, we aim to validate the utility of WSI in thyroid FNAs employing the Delphi method strategy. METHODS: A panel of experts from seven reference cytology centres was recruited. The study consisted of two consecutive rounds: (1) an open-ended, free-response questionnaire generating a list of survey items; and (2) a consensus analysis of 80 selected shared WSIs from 80 cases by six investigators answering six morphological questions utilising a 1 to 5 Likert scale. RESULTS: High consensus was achieved for all parameters, with an overall average score of 4.27. The broad majority of items (84%) were ranked either 4 or 5 by each physician. Two badly scanned cases were responsible for more than half of the low-ranked (≤2) values (57%). Good to excellent (≥3) diagnostic confidence was reached in more than 95.2% of cases. For most cases (78%) WSI assessment was not limited by technical issues linked to the image acquisition process. CONCLUSION: This systematic Delphi study indicates broad consensus among participating physicians on the application of DP to thyroid cytopathology, supporting expert opinion that WSI is reliable and safe for primary diagnostic purposes.

E-PSMA: the EANM standardized reporting guidelines v1.0 for PSMA-PET.

RATIONALE: The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions. METHODS: A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process. RESULTS: According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET. CONCLUSIONS: The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus.

BACKGROUND: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. METHODS: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. RESULTS: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. CONCLUSIONS: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.

Challenges with Implementing the Centers for Disease Control and Prevention Opioid Guideline: A Consensus Panel Report.

BACKGROUND: A national crisis of opioid-related morbidity, mortality, and misuse has led to initiatives to address the appropriate role of opioids to treat pain. Deployment of a guideline from the Centers for Disease Control and Prevention to reduce the risks of opioid therapy has raised substantial clinical and public policy challenges. The agency anticipated implementation challenges and committed to reevaluating the guideline for intended and unintended effects on clinician and patient outcomes. OBSERVATIONS: A multidisciplinary expert panel met to review the influence of the core recommendations of the guideline on pain management practices, principally regarding the estimated 5 to 8 million Americans with chronic pain currently on opioids. The panel identified implementation challenges, including application of dosage ceilings and prescription duration guidance, failure to appreciate the importance of patient involvement in decisions to taper or discontinue opioids, barriers to diagnosis and treatment of opioid use disorder, and impeded access to recommended comprehensive, multimodal pain care. Furthermore, policy-making and regulatory bodies may misapply guideline recommendations without flexibility and, sometimes, without full awareness of what the guideline contains. CONCLUSIONS AND RELEVANCE: The panel largely supported the guideline, endorsing its focal points of safety and comprehensive assessment and monitoring. To mitigate clinical and policy challenges identified with implementing the guideline, the panel discussed areas where viewpoints diverged and arrived at consensus proposals. The target audience includes the leaders and institutions that create policy and influence guideline implementation to include regulatory agencies, legislators, public and private payers, and health care systems.

A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017.

BACKGROUND: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk. The EAS Statement proposes that any mechanism of lowering plasma LDL concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C. However, as we explain, we do not find this conclusion acceptable. SUMMARY: Our review points out that different interpretations are possible for the results of Mendelian randomization studies. As for prospective cohort studies, many inconsistent reports on the association of LDL-C and ASCVD were disregarded when drafting the Statement, reports with and without genetic factors related to LDL receptor function should be analyzed separately, and the term ASCVD in the Statement is used inappropriately because myocardial infarction and cerebral infarction differ in their association with LDL-C. As for RCTs, clinical reports on statins published before and after the implementation of new regulations affecting clinical trials (2004/2005) should not both be included in meta-analyses because the evaluated efficacy of statins changed markedly, and the irreversible adverse effects of statins need to be evaluated more rigorously now that their mechanisms have been elucidated. Key Messages: Apart from the EAS hypothesis that LDL causes ASCVD, recent pharmacological/biochemical studies, as summarized in this review and elsewhere, have revealed that atherosclerosis is caused by statins taken to lower LDL-C, as well as by warfarin and some types of vegetable fats and oils, in the absence of significantly elevated LDL-C levels. Thus, the promotion of statin treatment by the Statement is rather risky and we do not feel that the conclusions are justified for the prevention of ASCVD.

Photobiomodulation with non-thermal lasers: Mechanisms of action and therapeutic uses in dermatology and aesthetic medicine.

BACKGROUND: Non-thermal laser therapy in dermatology, is a growing field in medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. OBJECTIVES: The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology. METHODS: A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis. RESULTS: The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N = 161), one prospective open-label study (N = 54), and two retrospective studies (N = 775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N = 38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N = 292). CONCLUSIONS: Non-thermal laser is steadily moving into mainstream medical practice, such as dermatology. Although present studies have demonstrated the safety and efficacy of non-thermal laser for body sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.

Consensus panel recommendations for the optimization of EPIDIOLEX® treatment for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Following the approval of Epidiolex® (cannabidiol; CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC), healthcare professionals (HCPs) have had substantial experience in treating patients with Epidiolex. However, confusion still remains among HCPs, caregivers, and patients regarding dosing, drug interactions, safety monitoring, and differentiation between Epidiolex and nonapproved CBD products. To establish consensus recommendations for Epidiolex treatment optimization in LGS, DS, and TSC, a panel of seven HCPs with expertise in epilepsy was convened. Panelists participated in a premeeting survey based on a literature review of Epidiolex for the treatment of LGS, DS, and TSC, and survey responses were compiled for discussion. A modified Delphi method was used to assess agreement among panelists regarding recommendation statements following two rounds of discussion. Panelists identified two broad themes - overcoming barriers to initiation and optimization of treatment for seizures associated with LGS, DS, and TSC - for consensus guidelines. Accurate identification of patients with these rare epilepsies is critical for optimization of Epidiolex treatment. Providers should differentiate Epidiolex from nonapproved CBD products and set expectations for the therapeutic effect and safety/tolerability of Epidiolex. Initial target dose and titration rate should be individualized by baseline variables, prior response to antiseizure medications, and therapeutic goals. Awareness of strategies to manage adverse events and concomitant medications, including drug-drug interactions, is critical. Tracking response to the maximum tolerated dose is an important measure of effectiveness. These consensus recommendations provide real-world experience from neurology HCPs with experience in prescribing Epidiolex and can inform optimal use of Epidiolex for the treatment of seizures associated with LGS, DS, and TSC. PLAIN LANGUAGE SUMMARY: Epidiolex® (cannabidiol) is approved for treating seizures in Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Although healthcare professionals have experience in treating patients with Epidiolex, there is a need for better understanding of dosing, drug interactions, and safety of this drug. Therefore, a group of epilepsy experts developed guidelines for best practices in Epidiolex treatment. Two main areas were identified: overcoming barriers to starting Epidiolex and considerations related to Epidiolex dosing. Within these areas, topics, including correct disease identification, managing adverse events, and determining individualized dose, were discussed. These guidelines provide real-world experience to inform optimal Epidiolex use.

Dosing Optimization of Low-Sodium Oxybate in Narcolepsy and Idiopathic Hypersomnia in Adults: Consensus Recommendations.

INTRODUCTION: Low-sodium oxybate (LXB) is approved for treatment of narcolepsy in patients aged 7 years and older and treatment of idiopathic hypersomnia in adults. LXB contains the same active moiety with 92% less sodium than sodium oxybate (SXB). As the indication for oxybate treatment in patients with idiopathic hypersomnia is new and allows for individualized dosing optimization, guidance for beginning LXB treatment is needed. In particular, clinicians may benefit from guidance regarding treatment initiation, dosing/regimen options, potential challenges, and treatment expectations. Additionally, pharmacokinetic profiles differ slightly between both treatments, and further guidance on transitioning from SXB to LXB in patients with narcolepsy may aid clinicians. METHODS: An expert panel of five sleep specialists was convened to obtain consensus on recommendations for these topics using a modified Delphi process. RESULTS: Across two virtual meetings, the panel agreed on 31 recommendations with a high degree of consensus that fell into four overarching topics: (1) introducing LXB to patients; (2) initiating LXB for adult narcolepsy and idiopathic hypersomnia; (3) addressing challenges in using LXB; and (4) transitioning from SXB to LXB. The panel recommended that clinicians provide a clear overview of how LXB works for treating symptoms in narcolepsy or idiopathic hypersomnia, as appropriate for their patients, explain safety aspects, and set expectations prior to initiating LXB treatment. Strategies for initial dosing and regimen are provided. Strategies for adjusting the dose, regimen, timing, and consideration of individual factors were developed for specific instances in which patients may have trouble staying asleep or waking up, as well as guidance for addressing potential adverse events, such as nausea, dizziness, anxiety, and depression. Discussion points based on existing literature and clinical experience were included as relevant for each statement. CONCLUSION: Clinicians may use this resource to guide LXB dosing optimization with patients.

Developing a questionnaire for assessing clinician- and patient-reported outcomes in actinic keratosis: Results from an expert panel.

Background: Current assessments on topical treatment attributes in actinic keratosis (AK) do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive AK-specific measures that fully capture the patient experience. Objective: To develop an actinic keratosis-specific expert panel questionnaire (AK-EPQ) of patient-reported outcomes and clinician-reported outcomes for use in research studies. Methods: Using interviews of patients with AK and targeted literature reviews, a 9-person consensus panel of dermatologists with expertise in AK treatment was convened to develop the AK-EPQ to assess AK-specific patient-reported outcomes and clinician-reported outcomes. Results: Nine expert advisers achieved consensus on 11 AK-EPQ items that encompass patient and clinician perspectives of treatment-related local skin reactions, clinical and cosmetic outcomes associated with AK, and satisfaction with treatment; the AK-EPQ will be first implemented in the Patient-Reported Outcomes for Actinic Keratosis study (NCT05260073). Limitations: The AK-EPQ does not directly measure quality of life, although it can be used with validated quality of life instruments. Conclusion: The newly developed AK-EPQ elicits insights into the patient and clinician experience with AK treatments. Comparative probing of these perspectives may help optimize precision medicine in AK treatment.

Determining clinically meaningful thresholds for innovative burn care products to reduce autograft: A US burn surgeon Delphi panel.

Reducing the amount of donor skin needed for definitive wound closure can improve outcomes in patients with severe burns. This Delphi Consensus Panel (DCP) aimed to achieve expert consensus on the percentage reduction in donor skin for autograft that constitutes a clinically meaningful benefit. A two-round DCP of fifteen US burn surgeons was conducted via a web-based survey platform. Fourteen panelists (93.3%) completed both rounds. In Round 2, consensus, defined as ≥70% agreement, was achieved for five of the seven consensus statements. All panelists agreed that a clinically meaningful reduction in the amount of donor skin required would facilitate wound management and decrease donor site morbidity experienced by patients. Furthermore, based on three treatment scenarios, consensus was achieved for a clinically meaningful reduction in the amount of donor skin required for autograft for the adult population in deep partial-thickness and full-thickness burns. Findings from this DCP indicate that an innovative cellular and/or tissue product that would reduce the needed amount of donor skin, by the identified thresholds, has the potential to improve the outcomes for patients with severe burn injuries in a meaningful way.

Role of patient and public involvement in implementation research: a consensus study.

BACKGROUND: Patient and public involvement (PPI) is often an essential requirement for research funding. Distinctions can be drawn between clinical research, which generally focuses on patients, and implementation research, which generally focuses on health professional behaviour. There is uncertainty about the role of PPI in this latter field. We explored and defined the roles of PPI in implementation research to inform relevant good practice guidance. METHODS: We used a structured consensus process using a convenience sample panel of nine experienced PPI and two researcher members. We drew on available literature to identify 21 PPI research roles. The panel rated their agreement with roles independently online in relation to both implementation and clinical research. Disagreements were discussed at a face-to-face meeting prior to a second online rating of all roles. Median scores were calculated and a final meeting held to review findings and consider recommendations. RESULTS: Ten panellists completed the consensus process. For clinical research, there was strong support and consensus for the role of PPI throughout most of the research process. For implementation research, there were eight roles with consensus and strong support, seven roles with consensus but weaker support and six roles with no consensus. There were more disagreements relating to PPI roles in implementation research compared with clinical research. PPI was rated as contributing less to the design and management of implementation research than for clinical research. CONCLUSIONS: The roles of PPI need to be tailored according to the nature of research to ensure authentic and appropriate involvement. We provide a framework to guide the planning, conduct and reporting of PPI in implementation research, and encourage further research to evaluate its use.

Development of the Pediatric Social Risk Instrument Using a Structured Panel Approach.

BACKGROUND: Social determinants of health impact child illness. Currently, no instrument exists to identify social need during hospital admission. METHODS: Using the UCLA (University of California Los Angeles)-RAND appropriateness method, consensus was reached for an instrument to identify social need in hospitalized children. A panel of 11 experts reviewed candidate indicators through 3 rounds to reach consensus. The instrument then underwent usability testing. RESULTS: Three hundred and forty-seven indicators from the literature were sorted into 18 social risk themes. After 3 rounds, consensus was reached on 82 indicators. Six additional social risk themes were recommended by the panel, resulting in consensus for 18 additional indicators. Final refinement resulted in an instrument containing 86 indicators representing 11 social risk themes. Usability testing identified that the tool was well received by families. Final feedback was incorporated into a post-usability instrument. CONCLUSIONS: Using the UCLA-RAND appropriateness method, a new pediatric social risk instrument was created to identify social need for hospitalized children.

Cardiac Autonomic Neuropathy in Diabetes Mellitus.

Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of patients with type 1 diabetes. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. The pathophysiology of CAN is complex, likely multifactorial, and not completely understood. Treatment is limited to symptomatic control of orthostatic hypotension, which is a late complication, and current strategies to reverse CAN are limited. This review explores the epidemiology, pathophysiology, clinical manifestations, diagnosis, and complications of CAN as well as current treatment options.

Methodology to reliably measure preventable trauma death rate.

This article describes a methodology to establish a trauma preventable death rate (PDR) in a densely populated county in the USA. Harris County has >4 million residents, encompasses a geographic area of 1777 square miles and includes the City of Houston, Texas. Although attempts have been made to address a national PDR, these studies had significant methodological flaws. There is no national consensus among varying groups of clinicians for defining preventability or documenting methods by which preventability is determined. Furthermore, although trauma centers routinely evaluate deaths within their hospital for preventability, few centers compare across regions, within the prehospital arena and even fewer have evaluated trauma deaths at non-trauma centers. Comprehensive population-based data on all trauma deaths within a defined region would provide a framework for effective prevention and intervention efforts at the regional and national levels. The authors adapted a military method recently used in Southwest Asia to determine the potential preventability of civilian trauma deaths occurring across a large and diverse population. The project design will allow a data-driven approach to improve services across the entire spectrum of trauma care, from prevention through rehabilitation.

Estimating healthcare resource use associated with the treatment of metastatic melanoma in eight countries.

Objectives Studies reporting healthcare resourse use (HRU) for melanoma, one of the most costly cancers to treat, are limited. Using consistent, robust methodology, this study estimated HRU associated with the treatment of metastatic melanoma in eight countries. Methods Using published literature and clinician input, treatment phases were identified: active systemic treatment (pre-progression); disease progression; best supportive care (BSC)/palliative care; and terminal care. HRU elements were identified for each phase and estimates of the magnitude and frequency of use in clinical practice were obtained through country-specific Delphi panels, comprising healthcare professionals with experience in oncology (n = 8). Results Medical oncologists are the key care providers for patients with metastatic melanoma, although in Germany dermato-oncologists also lead care. During the active systemic treatment phase, each patient was estimated to require 0.83-2 consultations with a medical oncologist/month across countries; the median number of such assessments in 3 months was highest in Canada (range = 3.5-5) and lowest in France, the Netherlands and Spain (1). Resource use during the disease progression phase was intensive and similar across countries: all patients were estimated to consult with medical oncologists and 10-40% with a radiation oncologist; up to 40% were estimated to require a brain MRI scan. During the BSC/palliative care phase, all patients were estimated to consult with medical oncologists, and most to consult with a primary care physician (40-100%). Limitations Panelists were from centers of excellence, thus results may not reflect care within smaller hospitals; data obtained from experts may be less variable than data from broader clinical practice. Treatments for metastatic melanoma are continually emerging, thus some elements of our work could be superseded. Conclusions HRU estimates were substantial and varied across countries for some resources. These data could be used with country-specific costs to elucidate costs for the management of metastatic melanoma.