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Summary: Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune‐mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil‐predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. Aims: To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non‐EoE EGIDs, and discuss key remaining knowledge gaps. Methods: We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta‐analyses. Results: Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non‐EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. Conclusions: Unmet needs for research are dramatically different for EoE and non‐EoE EGIDs. In EoE, non‐invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non‐EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders. [ABSTRACT FROM AUTHOR]

Background: Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. Methods: We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high‐resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. Key Results: Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2) and EGJOO (1.2 mmHg/mm2) versus type 2 (2.3 mmHg/mm2) and type 1 achalasia (2.9 mmHg/mm2). Conclusions: Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation. [ABSTRACT FROM AUTHOR]

Background: Myotomy length in type 3 achalasia is generally tailored based on segment of spasticity on high‐resolution manometry (HRM). Potential of length of tertiary contractions on barium esophagram (BE) or length of thickened circular muscle on endoscopic ultrasound (EUS) to guide tailored myotomy is less understood. This study aimed to assess agreement between spastic segments lengths on HRM, BE, and EUS among patients with type 3 achalasia. Methods: This retrospective study included adults with type 3 achalasia on HRM between November 2019 and August 2022 who underwent evaluation with EUS and/or BE. Spastic segments were defined as HRM—distance between proximal borders of lower esophageal sphincter and high‐pressure area (isobaric contour ≥70 mmHg); EUS—length of thickened circular muscle (≥1.2 mm) from proximal border of esophagogastric junction (EGJ) to the transition to a non‐thickened circular muscle; BE—distance between EGJ to proximal border of tertiary contractions. Pairwise comparisons assessed for correlation (Pearson's) and intraclass correlation classification (ICC) agreement. Key Results: Twenty‐six patients were included: mean age 66.9 years (SD 13.8), 15 (57.7%) male. Spastic segments were positively correlated on HRM and BE with good agreement (ICC 0.751, [95% CI 0.51, 0.88]). Spastic segments were negatively correlated with poor agreement on HRM and EUS (ICC −0.04, [−0.45, 0.39]) as well as BE and EUS (ICC −0.03, [−0.47, 0.42]). Conclusions & Inferences: Length of spastic segment was positively correlated on HRM and BE while negatively correlated when compared to EUS, supporting the common use of HRM and highlighting the uncertain role for EUS in tailoring myotomy length for type 3 achalasia. [ABSTRACT FROM AUTHOR]

Background: Patient and public involvement in health economic evaluation is still relatively rare, compared to other areas of health and social care research. Developing stronger patient and public involvement in health economic evaluation will be important in the future because such evaluations can impact on the treatments and interventions that patients can access in routine care. Main text: The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) is a reporting guideline for authors publishing health economic evaluations. We established an international group of public contributors who were involved in the update of the CHEERS 2022 reporting guidance, ensuring two items (areas of reporting) specifically about public involvement were included. In this commentary we focus on the development of a guide to support public involvement in reporting, a key suggestion made by the CHEERS 2022 Public Reference Group, who advocated for greater public involvement in health economic evaluation. This need for this guide was identified during the development of CHEERS 2022 when it became apparent that the language of health economic evaluation is complex and not always accessible, creating challenges for meaningful public involvement in key deliberation and discussion. We took the first step to more meaningful dialogue by creating a guide that patient organisations could use to support their members to become more involved in discussions about health economic evaluations. Conclusions: CHEERS 2022 provides a new direction for health economic evaluation, encouraging researchers to undertake and report their public involvement to build the evidence base for practice and may provide some reassurance to the public that their voice has played a part in evidence development. The CHEERS 2022 guide for patient representatives and patient organisations aims to support that endeavour by enabling deliberative discussions among patient organisations and their members. We recognise it is only a first step and further discussion is needed about the best ways to involve public contributors in health economic evaluation. Background: Patient and public involvement in health economic evaluation is still relatively rare, compared to other areas of health and social care research. Developing stronger patient and public involvement in health economic evaluation will be important in the future because such evaluations can impact on the treatments and interventions that patients can access in routine care. Main text: We established an international group of public contributors who were involved in the development of the CHEERS 2022 reporting guidance, ensuring two items (areas of reporting) specifically about patient and public involvement were included. In this commentary we focus on the development of a guide to support patient and public involvement in reporting, a key suggestion made by the CHEERS 2022 Public Reference Group, who advocated for greater public involvement in health economic evaluation. The need for this guide was identified during the development of CHEERS 2022 when it became apparent that the language of health economic evaluation is complex and not always accessible, creating challenges for meaningful public involvement in key deliberation and discussion. We took the first step to more meaningful dialogue by creating a guide that patient representatives and patient organisations could use as support to become more involved in discussions about health economic evaluations. Conclusions: CHEERS 2022 provides a new direction for health economic evaluation, encouraging researchers to undertake and report their public involvement in order to build the evidence base for practice. The CHEERS 2022 guide aims to support patient representatives and patient organisations to become more involved in discussions about health economic evaluations. We recognise it is only a first step and further discussion is needed about the best ways to involve public contributors in health economic evaluation. [ABSTRACT FROM AUTHOR]

Background: Panesophageal pressurization (PEP) defines type II achalasia on high‐resolution‐manometry (HRM) but some patients exhibit spasm after treatment. The Chicago Classification (CC) v4.0 proposed high PEP values as predictor of embedded spasm, yet supportive evidence is lacking. Methods: Fifty seven type II achalasia patients (47 ± 18 years, 54% males) with HRM and LIP Panometry before and after treatment were retrospectively identified. Baseline HRM and FLIP studies were analyzed to identify factors associated with post‐treatment spasm, defined on HRM per CC v4.0. Results: Seven patients (12%) had spasm following treatment (peroral endoscopic myotomy 47%; pneumatic dilation [PD] 37%; laparoscopic Heller myotomy 16%). At baseline, greater median maximum PEP pressure (MaxPEP) values on HRM (77 vs 55 mmHg, p = 0.045) and spastic‐reactive contractile response pattern on FLIP (43% vs 8%, p = 0.033) were more common in patients with post‐treatment spasm while absent contractile response on FLIP was more common in patients without spasm (14% vs 66%, p = 0.014). The strongest predictor of post‐treatment spasm was the percentage of swallows with MaxPEP ≥70 mmHg (best cut‐off: ≥30%), with AUROC of 0.78. A combination of MaxPEP <70 mmHg and FLIP 60 mL pressure < 40 mmHg identified patients with lower rates of post‐treatment spasm (3% overall, 0% post‐PD) compared to those with values above these thresholds (33% overall, 83% post‐PD). Conclusions: High maximum PEP values, high FLIP 60 mL pressures and contractile response pattern on FLIP Panometry prior to treatment identified type II achalasia patients more likely to exhibit post‐treatment spasm. Evaluating these features may guide personalized patient management. [ABSTRACT FROM AUTHOR]

Purpose of Review: While guidelines exist for the evaluation and management of esophageal dysphagia in the general population, dysphagia disproportionately affects the elderly. In this article, we reviewed the literature on evaluating esophageal dysphagia in elderly patients and proposed a diagnostic algorithm based on this evidence. Recent Findings: In older patients, dysphagia is often well compensated for by altered eating habits and physiologic changes, underreported by patients, and missed by healthcare providers. Once identified, dysphagia should be differentiated into oropharyngeal and esophageal dysphagia to guide diagnostic workup. For esophageal dysphagia, this review proposes starting with endoscopy with biopsies, given its relative safety even in older patients and potential for interventional therapy. If endoscopy shows a structural or mechanical cause, then further cross-sectional imaging should be considered to assess for extrinsic compression, and same session endoscopic dilation should be considered for strictures. If biopsies and endoscopy are normal, then esophageal dysmotility is more likely, and high-resolution manometry and additional workup should be performed following the updated Chicago Classification. Even after diagnosis of the root cause, complications including malnutrition and aspiration pneumonia should also be assessed and monitored, as they both result from and can further contribute to dysphagia. Summary: The successful evaluation of esophageal dysphagia in elderly patients requires a thorough, standardized approach to collecting a history, selection of appropriate diagnostic workup, and assessment of risk of potential complications, including malnutrition and aspiration. [ABSTRACT FROM AUTHOR]

Purpose of review: We review and summarize current evidence-based management strategies for non-achalasia esophageal hypercontractility disorders: esophagogastric junction outflow obstruction (EGJOO) and hypercontractile esophagus. Recent findings: EGJOO. Per Chicago Classifications version 4.0 (CCv4.0), current diagnostic criteria for EGJOO require conclusive manometric findings, clinically relevant symptoms plus at least one supportive test confirming obstruction (either timed barium esophagram (TBE) or functional lumen imaging probe (FLIP)). Hypercontractile esophagus. Per CCv4.0, current diagnostic criteria for hypercontractile esophagus requires conclusive manometric findings in addition to clinically relevant symptoms. Three identifiable sub-groups of hypercontractile esophagus include single-peak hypercontractility, Jackhammer esophagus, and hypercontractile with LES after-contraction. Summary: Updates in CCv4.0 focus on distinguishing clinically relevant esophageal disorders from manometric patterns alone. As definitive therapies for esophageal disorders are limited, current approaches to treatment focus on achieving symptom relief with conservative modalities prior to attempting more invasive therapies. [ABSTRACT FROM AUTHOR]

In the past, the Cratoxylum genus has often been utilized as traditional medicines, culinary ingredients, health supplements, as well as manufacturing materials. This flowering plant belongs to the family Hypericaceae and is classified into six species: Cratoxylum arborescens, Cratoxylum cochinchinense, Cratoxylum formosum, Cratoxylum glaucum, Cratoxylum maingayi, and Cratoxylum sumatranum. The Cratoxylum genus is native to Asia as a traditional medicinal plant. It is currently being translated into conventional therapeutics as a preventive agent for diabetes mellitus and cardiovascular diseases. The phytochemical analysis and pharmacological investigations on the Cratoxylum species have unveiled the wide spectrum of phytoconstituents, including xanthones, triterpenoids, flavonoids, and phenolic compounds. These compounds are attributed to their significant pharmacological effects, such as antibacterial, antifungal, antioxidant, antimalarial, anti-gastric ulcer, anti-HIV-1 reverse transcriptase, antidiabetic, and anticancer activities. These research findings have strengthened the foundation of the Cratoxylum genus as a traditional medicinal plant to be further developed and applied as selective therapeutic drugs for various ailments. This paper discusses the Cratoxylum genus regarding its traditional uses, phytochemical compounds, and pharmacological properties. [ABSTRACT FROM AUTHOR]

Background: Type II achalasia (Ach2) is distinguished from other achalasia sub‐types by the presence of panesophageal pressurization (PEP) of ≥30 mmHg in ≥20% swallows on high‐resolution manometry (HRM). Variable manometric features in Ach2 have been observed, characterized by focal elevated pressures (FEPs) (focal/segmental pressures ≥70 mmHg within the PEP band) and/or high compression pressures (PEP ≥70 mmHg). This study aimed to examine clinical and physiologic variables among sub‐groups of Ach2. Methods: This retrospective single center study performed over 3 years (1/2019–1/2022) included adults with Ach2 on HRM who underwent endoscopic ultrasound (EUS), functional lumen imaging probe (FLIP), and/or barium esophagram (BE) prior to therapy. Patients were categorized into two overarching sub‐groups: Ach2 without FEPs and Ach2 with FEPs. Demographic, clinical, and physiologic data were compared between these sub‐groups utilizing unpaired univariate analyses. Key Results: Of 53 patients with Ach2, 40 (75%) were without FEPs and 13 (25%) had FEPs. Compared with the Ach2 sub‐group without FEPs, the Ach2 sub‐group with FEPs demonstrated a significantly thickened distal esophageal circular muscle on EUS (1.4 mm [SD 0.9] vs. 2.1 [0.7]; p = 0.02), higher prevalence of tertiary contractions on BE (46% vs. 100%; p = 0.0006), lower esophagogastric junction distensibility index (2.2mm2/mmHg [0.9] vs 0.9 [0.4]; p = 0.0008) as well as higher distensive pressure (31.0 mmHg [9.8] vs. 55.4 [18.8]; p = 0.01) at 60 cc fill on FLIP, and higher prevalence of chest pain on Eckardt score (p = 0.03). Conclusions and Inferences: We identified a distinct sub‐group of type II achalasia on HRM, defined as type II achalasia with focal elevated pressures. This sub‐group uniquely exhibits spastic features and may benefit from personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc.). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making. [ABSTRACT FROM AUTHOR]

Aims: The population prevalence of cardiomyopathies and the natural history of symptomatic heart failure (HF) and arrhythmia across cardiomyopathy phenotypes is poorly understood. Study aims were to estimate the population-diagnosed prevalence of cardiomyopathies and describe the temporal relationship between a diagnosis of cardiomyopathy with HF and arrhythmia.Methods: People with cardiomyopathy (n=4116) were identified from linked electronic health records (~9 million individuals; 2000-2018) and categorised into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM) and cardiac amyloidosis (CA). Cardiomyopathy point prevalence, rates of symptomatic HF and arrhythmia and timing relative to a diagnosis of cardiomyopathy were determined.Results: In 2018, DCM was the most common cardiomyopathy. DCM and HCM were twice as common among men, with the reverse trend for ARVC. Between 2010 and 2018, prevalence increased for ARVC by 180% and HCM by 9%. At diagnosis, more patients with CA (66%), DCM (56%) and RCM (62%) had pre-existing HF compared with ARVC (29%) and HCM (27%). Among those free of HF at diagnosis of cardiomyopathy, annualised HF incidence was greatest in CA and DCM. Diagnoses of all cardiomyopathies clustered around the time of HF onset.Conclusions: The recorded prevalence of all cardiomyopathies increased over the past decade. Recognition of CA is generally preceded by HF, whereas individuals with ARVC or HCM more often developed HF after their cardiomyopathy diagnosis suggesting a more indolent course or better asymptomatic recognition. The clustering of HF and cardiomyopathy diagnoses suggests opportunities for presymptomatic or earlier diagnosis. [ABSTRACT FROM AUTHOR]

Over the past decade, the landscape of achalasia diagnosis, and particularly achalasia treatment, has broadened. QI adherence was assessed on three domains: achalasia diagnosis, achalasia treatment, and patient education. Meteoric advancements in medical science and technology have exceeded the ability of the healthcare delivery system to provide consistently high-quality care to patients. [Extracted from the article]

Blown-out myotomy: an adverse event of laparoscopic Heller myotomy and peroral endoscopic myotomy for achalasia. Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation. [Extracted from the article]

Summary: Multiple myeloma is associated with significant early morbidity and mortality, with considerable end organ damage often present at diagnosis. The Tackling EArly Morbidity and Mortality in Multiple Myeloma (TEAMM) trial was used to evaluate routes to diagnosis in patients with myeloma and the relationship between diagnostic pathways, time to diagnosis and disease severity. A total of 915 participants were included in the study. Fifty‐one per cent were diagnosed by direct referral from primary care to haematology; 29% were diagnosed via acute services and 20% were referred via other secondary care specialties. Patients diagnosed via other secondary care specialties had a longer diagnostic interval (median 120 days vs. 59 days) without an increase in features of severe disease, suggesting they had a relatively indolent disease. Marked intrahospital delay suggests possible scope for improvement. A quarter of those diagnosed through acute services reported >30 days from initial hospital consultation to haematology assessment. Participants diagnosed through acute services had poorer performance status (P < 0·0001) and higher burden of end organ damage (P < 0·0001) with no difference in the overall length of diagnostic pathway compared to those diagnosed by direct referral (median 59 days). This suggests that advanced disease in patients presenting through acute services predominantly reflects disease aggression. [ABSTRACT FROM AUTHOR]

Chagas' disease achalasia may represent a sub-group of type 2 achalasia without focal elevated pressures Neuronal destruction patterns in Chagas' disease achalasia differ from idiopathic achalasia. The blue arrows represent FEPs within the PEP band. gl Chagas' disease achalasia may represent a type 2 achalasia sub-group I without i FEPs which may be consistent with a dilated, non-spastic esophagus. [Extracted from the article]

The article focuses on the feasibility in the use of the inhibitor Panobinostat in patients with relapsed multiple myeloma (MM) alongside dexamethasone and bortezomib. It talks about the clinical trial for progression-free survival (PFS) in patients going through disease relapse. It tells about the need to improve the efficiency of the drugs Dexamethasone, Bortezomib and Thalidomide alongside the inhibitor.

Introduction: Patient preferences (PPs) are an important source of evidence in health technology assessment (HTA). However, a methodological framework to achieve their integration in decision-making is lacking. We aim to investigate the potential role of evaluative frameworks to integrate PP evidence into HTA and decision-making. Methods: We undertook a scoping review to identify potential methodological frameworks to consider PP evidence in HTA and evidence of the acceptability of these frameworks for decision-makers. We searched PubMed, Cochrane, and the grey literature to identify relevant studies, reports, or guidance documents. We restricted our search to the use of PP rather than patient experience data and excluded articles solely relating to deliberative approaches. Results: Frameworks identified as having the potential to integrate PP evidence included cost-utility analysis, cost-consequence analysis (CCA), the efficiency-frontier approach, and multi-criteria decision analysis. All have been used in various HTA contexts, but not necessarily for inclusion of PP evidence. Distinct benefits and challenges of integrating PP data were identified for each framework. These included the theoretical basis of the frameworks, their ability to consider non-health as well as health outcomes, and their ability to separate outcomes based on PPs from outcomes based on population preferences. There is limited evidence and no consensus on the application of these frameworks to consider PPs in HTA or on their acceptability for decision-makers. However, CCA has the advantage that it is both based on economic decision theory and it leaves patient preferences disaggregated from population preferences in an HTA. Conclusions: The frameworks identified in this review offer potential approaches to systematically and transparently integrate PPs into HTA and decision-making. Based on the review findings, we propose a research agenda to explore the potential of CCA in particular. We anticipate that our findings will augment the recommendations of the Innovative Medicines Initiative PREFER project, which are expected to report in 2022. [ABSTRACT FROM AUTHOR]

Abstract: Background: The objectives of this study were to elicit the preferences of patients with multiple myeloma regarding the possible benefits and risks of cancer treatments and to illustrate how such data may be used to estimate patients’ acceptance of new treatments. Patients and Methods: Patients with multiple myeloma from the cancer charity Myeloma UK were invited to participate in an online survey based on multicriteria decision analysis and swing weighting to elicit individual stated preferences for the following attributes: (a) 1‐year progression‐free survival (PFS, ranging from 50% to 90%), (b) mild or moderate toxicity for 2 months or longer (ranging from 85% to 45%), and (c) severe or life‐threatening toxicity (ranging from 80% to 20%). Results: A total of 560 participants completed the survey. The average weight given to PFS was 0.54, followed by 0.32 for severe or life‐threatening toxicity and 0.14 for mild or moderate chronic toxicity. Participants who ranked severe or life‐threatening toxicity above mild or moderate chronic toxicity (56%) were more frequently younger, working, and looking after dependent family members and had more frequently experienced severe or life‐threatening side effects. The amount of weight given to PFS did not depend on any of the collected covariates. The feasibility of using the collected preference data to estimate the patients’ acceptance of specific multiple myeloma treatments was demonstrated in a subsequent decision analysis example. Conclusion: Stated preference studies provide a systematic approach to gain knowledge about the distribution of preferences in the population and about what this implies for patients’ acceptance of specific treatments. Implications for Practice: This study demonstrated how quantitative preference statements from a large group of participants can be collected through an online survey and how such information may be used to explore the acceptability of specific treatments based on the attributes studied. Results from such studies have the potential to become an important new tool for gathering patient views and studying heterogeneity in preferences in a systematic way, along with other methods, such as focus groups and expert opinions. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Visaggi et al papers. To view these articles, visit https://doi.org/10.1111/apt.17101 [ABSTRACT FROM AUTHOR]

A growing population of long-term survivors of myeloma is now accumulating the 'late effects' not only of myeloma itself, but also of several lines of treatment given throughout the course of the disease. It is thus important to recognise the cumulative burden of the disease and treatment-related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long-term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late-effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Some countries make considerable effort to involve patients and patient groups in their health technology assessment (HTA) processes; others are only just considering or are yet to consider patient involvement in HTA.Methods: This commentary offers four arguments why patient involvement should be prioritized by those HTA agencies that do not yet involve patients: (1) from a patients' rights perspective, (2) based on patient and community values, (3) centering on evidentiary contributions, and (4) from a methodological perspective.Results: The first argument builds on the Alma-Ata Declaration, which holds that patients have a right and duty to have a say in the planning and delivery of their health care, individually and collectively. Where HTA is used to determine access to technologies and services, we argue that patients have a right to be heard. The second argues that decisions about treatments and services need to be aligned with the core values and morals of the patients whom the health system serves. The third argues that patients have unique knowledge and insights about living with a health condition and their needs for services and treatments regarding that condition, which can add to the knowledge base and value of the HTA process. The fourth argues that involvement of patients can facilitate methodological advancement of HTA, in areas such as early scientific advice and managed entry with evidence development.Conclusions: An HTA process that includes patient perspectives can, therefore, provide added value to patients, policy makers and healthcare professionals alike. [ABSTRACT FROM AUTHOR]

Introduction: The number of patient preference studies in health has increased dramatically. There is growing use of patient preferences in a wide variety of contexts, including health technology assessment. Patient preference studies can help inform decision makers on the needs and priorities of patients and the tradeoffs they are willing to make about health technologies. Methods: This International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force included international experts, health preference researchers and others from diverse backgrounds, including regulatory, health technology assessment, medicine, patient advocacy, and the pharmaceutical industry. The report underwent two rounds of written reviews by ISPOR Preferences Special Interest Group members until a final consensus was reached. The Task Force focused on developing a roadmap that would: (i) apply to the wide variety of preference methods, (ii) identify key domains to guide researchers and other stakeholders in making patient preference studies more useful to decision makers, and (iii) detail important questions to guide researchers conducting preference studies and those critically appraising them. Results: This Task Force report provides a novel roadmap that invites patient-preference researchers to work with decision makers, patients and other stakeholders to do even more to ensure that studies are useful and impactful. The ISPOR Roadmap consists of five key elements: (i) Context; (ii) Purpose; (iii) Population; (iv) Method; and (v) Impact. In this report, we define these five elements and provide good practices on how patient-preference researchers can actively contribute to increasing the usefulness and impact of patient preference studies in decision-making. We also present a set of key questions that can support researchers and other stakeholders in assessing efforts that promote preference studies' intended and unintended impact. Conclusions: This roadmap can help increase the usefulness and impact of patient preference studies in decision-making by challenging researchers to engage and partner with decision makers, patients and others, and together consider the intended and unintended impacts of patient preference studies on decision-making while actively fostering positive impact. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. Methods: MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ⩾ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. Discussion: The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. [ABSTRACT FROM AUTHOR]

In November 2014 the International Myeloma Working Group ( IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple myeloma without any of the traditional ' CRAB' (hyper calcaemia, renal impairment, anaemia, bone disease) end organ damage criteria but with one of three new criteria would be recommended to start treatment. Previously, the standard of care for such patients was expectant management. These three new criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum free light chain ( sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and greater than one unequivocal focal lesion on advanced imaging (low dose whole body computerized tomography, magnetic resonance imaging, 18F fluorodeoxyglucose positron emission tomography). Although this would appear to affect a small number of patients, the impact of these changes are broad, leading to an increased use of advanced imaging, a debate around the management of patients previously diagnosed with smouldering myeloma, changed terminology and clinical trial design and an extension of the use of biomarkers. For the first time the philosophy of treatment in myeloma will change from treatment initiation only being triggered by overt end organ damage to an era where sub clinical risk factors will also be taken into account. [ABSTRACT FROM AUTHOR]

Aim: Human embryonic stem cell (hESC)-derived motor neurons (MNs) can model neurodegenerative diseases, in other words, for the development of cell-based drug screening assays. However, efficient MN generation is challenging and high level of contamination of undifferentiated cells remains a significant problem when culturing hESC-derived MNs. We describe a protocol for the removal of undifferentiated cells using the DNA synthesis inhibitor arabinofuranosyl cytidine (Ara-C). Materials & methods: hESC-MNs were treated with Ara-C after the last step of differentiation. FACS analysis and fluorescence microscopy were used to identify and quantify MNs. Results: HB9/ChAT-positive live mature MNs were enriched 3.9-times in Ara-C-treated cultures when compared with untreated cells. The Ara-C-treated MNs are electrophysiologically functional and discharge action potentials. Conclusion: Ara-C selection of MNs can be combined with stem cell differentiation protocols to enrich MNs in culture. [ABSTRACT FROM AUTHOR]

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011. [ABSTRACT FROM AUTHOR]

The article offers information on the guidelines for the diagnosis and management of multiple myeloma in 2011 as recommended by the U.S. Agency for Healthcare Research and Quality. The annual incidence of myeloma in Great Britain is approximately 60-70 per million. The overall prevalence is likely to be increasing given the recently published data demonstrating improved survival rates over the last decade. Investigation of a patient with suspected myeloma should include the screening tests.

The article presents a guideline to provide healthcare professionals with clear guidance for the effective clinical investigation of patients with newly detected M-proteins. It offers them the practical management of patients with monoclonal gammopathy of undetermined significance (MGUS). This article also discusses the background of MGUS and provides information on M-proteins.

The article throws light on guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma. Most patients with plasma cell neoplasia have generalized disease at diagnosis, i.e. multiple myeloma (MM). However, a minority of patients with plasma cell malignancies present with either a single bone lesion, or less commonly, a soft tissue mass, of monoclonal plasma cells: solitary bone plasmacytoma (SBP) or extramedullary plasmacytoma (SEP). The primary treatment for most of the patients will be radiotherapy, but surgery may be required.

A letter to the editor related to the guidelines for the diagnosis and management of multiple myeloma including use of fluorescence in situ hybridization, autologous stem cell transplant and administration of bortezomib through injection.

The article presents information on a survey on the incidence of biphosphonates-associated jaw osteonecrosis in Great Britain. A postal survey of 648 healthcare professionals in the nation was conducted between Spring and Autumn in 2006, which included the details of their experience of treating myeloma using bisphosphonates during 2004 and 2005.

This article gives a patient organization's perspective on health technology assessments (HTAs) and the role that such organizations can, and should, play in them. [ABSTRACT FROM PUBLISHER]

The author reflects on the actual situation of patients suffering from myeloma in Great Britain. He cites a Myeloma UK survey which illustrates the fact the three quarters of physicians treating the disease have had their applications for a preferred treatment option rejected by primary care trusts because of high costs. To help these patients get well, he suggests the National Health Service (NHS) to pay part for their treatment. He says that NHS must use its resources well.