Evaluating therapeutic benefits of ubrogepant via latent class models: A post hoc exploratory analysis of the ACHIEVE I and ACHIEVE II trials

Objective

To evaluate an alternative method of defining acute treatment success in migraine by combining multiple indicators into a single dichotomous measure of success.

Background

Migraine is characterized by a symptom complex; combining these features as a single endpoint may improve the measurement of treatment effects and better predict patient satisfaction with treatment.

Methods

We used a confirmatory latent class model (LCM) with two latent classes interpreted as treatment success and treatment failure. Pooled data for placebo and ubrogepant 50 mg from the ACHIEVE I and ACHIEVE II trials and data for ubrogepant 100 mg from ACHIEVE I were used. LCM inputs included pre-dose and 2-h post-dose measures of pain severity (0–3), the presence/absence of associated symptoms (nausea, photophobia, and phonophobia [0 or 1]), and functional disability (0–3). All definitions were validated against satisfaction with study medication (SWSM) at 24 h post-dose; results were compared with 2-hour pain freedom (2hPF).

Results

This pooled analysis included 2247 participants. At 2 h post-dose in the ubrogepant 50 and 100 mg dose groups, 53.2% (472/887) and 54.9% (246/448) of participants, respectively, were classified as achieving treatment success using the LCM-based approach, compared to 39.0% (356/912) of participants in the placebo group. The results for treatment success using the 2hPF endpoint were 20.7% (184/887) and 21.5% (96/447) in the ubrogepant 50 and 100 mg dose groups, respectively, compared to 12.7% (116/912) for placebo. Using 24-h SWSM as an external validator, the LCM approach sensitivity and correct classification rates were higher than for 2hPF.

Conclusion

The LCM approach led to higher rates of treatment success and greater separation between ubrogepant and placebo and was a more sensitive predictor of treatment satisfaction than the regulatory endpoint of 2hPF.     

A close association of freedom from pain,migraine-related functional disability,and other outcomes: results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN

BackgroundWhile pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.MethodsPatient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.ResultsPatients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.ConclusionsThis study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.Trial RegistrationSAMURAI ({"type":"clinical-trial","attrs":{"text":"NCT02439320","term_id":"NCT02439320"}}NCT02439320); SPARTAN ({"type":"clinical-trial","attrs":{"text":"NCT02605174","term_id":"NCT02605174"}}NCT02605174).Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01303-w.     

慢性精神分裂症症状演变调查分析

目的 探讨反复发病且长期住院的慢性精神分裂症患者的症状演变情况。 方法 对104例符合《中国精神疾病分类方案与诊断标准》第三版(CCMD-3)精神分裂症诊断标准、病程≥5a的慢性精神分裂症患者,应用阳性症状量表(SAPS)和阴性症状量表(SANS)对以往和目前的精神症状进行评定。 结果 以往发病时以阳性精神症状发生率较高且丰富,目前以阴性精神症状较突出,两者间相比,24项症状中12项有极显著性差异(P<0.01),1项有显著差异(P<0.05)。 结论 慢性精神分裂症患者随着病程的迁延,阳性症状逐渐减少,而阴性症状逐渐突出,并进入慢性衰退期。     

癌症患者症状困扰的研究进展

文章指出了症状困扰对癌症患者生活质量及疾病康复的不良影响,并从概念、内涵、测量工具、特点、影响因素、对心理健康及生活质量的影响等方面对国内外癌症患者症状困扰的研究现状进行了系统的阐述。在此基础上,对国内症状困扰的研究进行了展望,并提出开发有效测评工具及扩大病种研究范畴等建议。     

腹腔镜胆囊大部切除术的临床应用体会附218例报告

目的：探讨腹腔镜胆囊大部切除术手术方法及临床价值。方法：回顾性分析2002年12月至2008年5月我科施行218例胆囊大部切除术患者的临床资料。结果：218例在腹腔镜下完成手术,本组病例中无死亡,无术后出血,无肝外胆道损伤,手术时间20至60分钟,平均35分钟,无中转开腹,未发现远期并发症。结论：在妥善处理残余胆囊并留置引流管的情况下,腹腔镜胆囊大部切除术是一种安全可行、创伤小、并发症少、术后恢复快的手术,具有较强的临床价值。     

Measuring symptom occurrence and symptom distress: development of the symptom experience index

AIM: This paper is a report of a study to assess reliability and construct validity of revised and refined version of the Adapted Symptom Distress Scale: the Symptom Experience Index (SEI). BACKGROUND: The development of the SEI, a 41-item Likert Scale assessing 20 symptoms, was based on self-regulation theory and an integrative conceptual analysis of symptom assessment and management. The model emphasizes the difference between the occurrence of a symptom (or multiple symptoms) and the distress (emotional) response to the occurrence of a symptom. It is the distress from symptom occurrence that promotes a person to take action and use known coping strategies to prevent the symptom occurrence or alleviate the distress from the symptom. METHOD: A contrast-group and test-retest approach was used to assess construct validity and reliability with a convenience sample of 158 patients at United States of America in 2003-2004. RESULTS: The SEI demonstrated reasonable internal consistency with a Cronbach's alpha of 0.91 for symptom experience, 0.85 for symptom occurrence and 0.84 for symptom distress. Test-retest reliability was supported by high intra-class correlation coefficients (symptom experience r = 0.93; symptom occurrence r = 0.94; symptom distress, r = 0.92). Construct validity was supported by statistically significant differences between patients and healthy adults. CONCLUSION: The SEI can be used as a baseline and outcome measure to assess the impact of multiple symptoms on patients, and the effectiveness of interventions to manage these symptoms.     

家族性与散发性精神分裂症患者前驱症状特征分析

目的探讨家族性与散发性精神分裂症患者前驱症状的临床特征,为临床防治提供依据。方法对31例有家族史的精神分裂症患者(家族组)和83例无家族史的精神分裂症患者(散发组),采用自拟的"家族性与散发性精神分裂症患者前驱症状及临床症状调查问卷"评定前驱症状,采用简明精神病量表、阴性症状量表和阳性症状量表评定精神症状,对两组评定结果进行对比分析。结果家族组多数起病缓慢,多无明显诱因,散发组多为急性起病且多有刺激诱因(P<0.05或0.01);两组情感、行为、思维和类神经衰弱方面的前驱症状发生率均无显著性差异(P均>0.05)。简明精神病量表、阴性症状量表和阳性症状量表评分均无显著性差异(P均>0.05)。结论家族性与散发性精神分裂症的病情表现较接近,前驱症状均较突出,早期识别有利于预防发病及早期干预。     

症状负担的概念分析

从词典、生理学、心理学、临床医学方面对症状负担概念进行分析,提出症状负担是一种主观感觉,症状的发生率、频率和严重程度给病人造成了生理负担,并且对病人的心理、精神造成多种负面影响。区分症状体验中多个与症状相关的概念,开发症状负担的评估工具,并制定准确的干预措施将会减轻病人的症状负担。     

精神分裂症患者脑脊液TRP/Tyr比值与临床特征分析

应用高压液相色谱(HPLC)对67例精神分裂症脑脊液中色氨酸(Tryptophan,TRP)和酪氨酸(Tyrosine,Try)进行测试,并引入TRP与其竞争性氨基酸(Competing amine acid,ComAA)比值概念并以其中位数分组,从而比较高比值和低比值组症状特症,结果发现高TRP/Tyr比值组的BPRS及其阳性症状显著高于低TRP/Tyr比值组,而两组阴性症状及非特异症状无差异,针对TRP/Tyr意义进行了讨论。     

Symptom Interactions as Mechanisms Underlying Symptom Pairs and Clusters

PURPOSE: To present a summary of the potential shared or interactive mechanisms underlying an exemplar symptom pair: sleep disturbances and pain. ORGANIZING CONSTRUCT: Understanding of the multidimensional shared and interactive mechanisms underlying symptoms pairs and clusters has the potential to enhance symptom management. METHODS: Reviews of the literature were conducted to search for information on shared or interactive mechanisms underlying sleep disturbances and pain; minimal data were available. Relevant information about individual symptoms was outlined and categorized in areas often used to describe the multidimensional nature of symptoms, including the physiological, psychological, behavioral, and sociocultural domains. This information was examined for relationships and commonalities. CONCLUSIONS: Many potential shared and interactive mechanisms underlying the symptom pair of sleep disturbances and pain were identified. These results indicate the need for further work and theory development in this area. The symptom interactional framework is a beginning conceptual perspective designed to facilitate this work. Implications for interdisciplinary translational research designed to optimize symptom management are discussed.     

癌症病人症状评估工具及他评研究进展

从常见症状、评估工具及方式方面介绍了癌症病人症状管理中的症状自评及他评研究现状,并对今后的研究方向进行了阐述。     

Advancing the science of symptom management

Since the publication of the original Symptom Management Model (Larson et al. 1994), faculty and students at the University of California, San Francisco (UCSF) School of Nursing Centre for System Management have tested this model in research studies and expanded the model through collegial discussions and seminars. AIM: In this paper, we describe the evidence-based revised conceptual model, the three dimensions of the model, and the areas where further research is needed. BACKGROUND/RATIONALE: The experience of symptoms, minor to severe, prompts millions of patients to visit their healthcare providers each year. Symptoms not only create distress, but also disrupt social functioning. The management of symptoms and their resulting outcomes often become the responsibility of the patient and his or her family members. Healthcare providers have difficulty developing symptom management strategies that can be applied across acute and home-care settings because few models of symptom management have been tested empirically. To date, the majority of research on symptoms was directed toward studying a single symptom, such as pain or fatigue, or toward evaluating associated symptoms, such as depression and sleep disturbance. While this approach has advanced our understanding of some symptoms, we offer a generic symptom management model to provide direction for selecting clinical interventions, informing research, and bridging an array of symptoms associated with a variety of diseases and conditions. Finally, a broadly-based symptom management model allows the integration of science from other fields.     

肺癌患者化疗期间的症状群及其对日常生活的影响

目的调查肺癌患者化疗期间的症状群及其对患者日常生活的影响。方法采用中文版安德森症状评估表对183例化疗期间的肺癌患者进行调查,通过因子分析提取肺癌患者化疗期间的症状群,通过回归分析探讨症状群对患者日常活动的影响。结果肺癌患者化疗期间存在胃肠道症状群、情绪症状群、疲乏相关症状群。三大症状群对患者日常活动的困扰有显著影响(P<0.01),可解释总变异的76.2%。结论肺癌患者症状发生频率高、程度重,存在多个症状群,并且严重影响日常活动。护士应该准确及时地进行症状评估,积极对症状群进行管理与控制,以改善患者的生活质量。     

用CES-D对非精神病患者的抑郁症状调查分析

为了解躯体病患者有无抑郁症状及程度,以便采取抗抑郁剂和开展心理治疗。采用流调用抑郁自评量表(CES-D),调查内科住院病人49例和患躯体疾病尚未住院的中年知识分子128人。结果发现CES-D量表总分>16分有64例,住院病人量表分显著高于未住院者。被调查者有36.2％(64/177)存在不同程度的抑郁症状,需抗抑郁剂及心理治疗。     

Stability of Symptom Clusters in Patients With Breast Cancer Receiving Chemotherapy

Context

Patients with breast cancer who undergo chemotherapy (CTX) experience between 10 and 32 concurrent symptoms. An evaluation of how these symptoms cluster together and how these symptom clusters change over time may provide insights into how to treat these multiple co-occurring symptoms.

Differences in the Symptom Experience of Older Oncology Outpatients

ContextThe relatively low number of older patients in cancer trials limits knowledge of how older adults experience symptoms associated with cancer and its treatment.ObjectivesThis study evaluated for differences in the symptom experience across four older age groups (60–64, 65–69, 70–74, ≥75 years).MethodsDemographic, clinical, and symptom data from 330 patients aged >60 years who participated in one Australian and two U.S. studies were evaluated. The Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, frequency, and distress of 32 symptoms commonly associated with cancer and its treatment.ResultsOn average, regardless of the age group, patients reported 10 concurrent symptoms. The most prevalent symptoms were physical in nature. Worrying was the most common psychological symptom. For 28 (87.5%) of the 32 Memorial Symptom Assessment Scale symptoms, no age-related differences were found in symptom occurrence rates. For symptom severity ratings, an age-related trend was found for difficulty swallowing. As age increased, severity of difficulty swallowing decreased. For symptom frequency, age-related trends were found for feeling irritable and diarrhea, with both decreasing in frequency as age increased. For symptom distress, age-related trends were found for lack of energy, shortness of breath, feeling bloated, and difficulty swallowing. As age increased, these symptoms received lower average distress ratings.ConclusionAdditional research is warranted to examine how age differences in symptom experience are influenced by treatment differences, aging-related changes in biological or psychological processes, or age-related response shift.