Comprehensive approach to reintegration of disability benefit recipients with multiple problems (CARm) into the labour market: results of a randomized controlled trial

2区 · 医学

Article

作者: Wilming, Loes ; Roelofs, Pepijn D. D. M. ; Brouwer, Sandra ; Stewart, Roy E. ; Hoekstra, Tialda ; Brongers, Kor A.

PURPOSE:

Although most clients on work disability benefits face multiple problems, most traditional interventions for (re)integration focus on a single problem. The aim of this study was to evaluate the "Comprehensive Approach to Reintegrate clients with multiple problems" (CARm), which provides a strategy for labour experts to build a relationship with each client in order to support clients in their needs and mobilize their social networks.

METHODS:

This study is a stratified, two-armed, non-blinded randomized controlled trial (RCT), with a 12-month follow-up period. Outcome measures were: having paid work, level of functioning, general health, quality of life, and social support.

RESULTS:

We included a total of 207 clients in our study; 97 in the intervention group and 110 in the care as usual (CAU) group. The clients' mean age was 35.4 years (SD 12.8), 53.1% were female, and 179 (86.5%) reported multiple problems. We found the CARm intervention to have no significant effects superior to those of the CAU group on all outcomes.

CONCLUSION:

As we found no superior effect of the CARm intervention compared to CAU, we cannot recommend widespread adoption of CARm. A process evaluation will give more insight into possible implementation failure of the intervention.IMPLICATIONS FOR REHABILITATIONMost traditional interventions for (re)integration into the labour market are problem-centred, i.e., focusing on a single problem, and have limited effectiveness in persons with multiple problems.A strength-based intervention may be suitable for vocational rehabilitation and disability settings, since it contains many elements (e.g., being strength-based, focused on clients' wishes and goals, and involving activation of the social environment) also likely to improve chances of re-employment of persons with multiple problems.In this study a strength-based intervention did not show a superior effect on paid employment and functioning within one year follow-up compared to care as usual in people with multiple problems on a work disability benefit.

2022-05-20·ACS synthetic biology2区 · 生物学

CRISPR-Cas Assisted Shotgun Mutagenesis Method for Evolutionary Genome Engineering

2区 · 生物学

Article

作者: Gao, Bei ; Gao, Miaomiao ; Liu, Min ; Zhao, Ming ; Tao, Xinyi ; Wei, Dong-Zhi ; Wang, Feng-Qing ; Liu, Yongjun ; Xiong, Liangbin

Genome mutagenesis drives the evolution of organisms. Here, we developed a CRISPR-Cas assisted random mutation (CARM) technique for whole-genome mutagenesis. The method leverages an entirely random gRNA library and SpCas9-NG to randomly damage genomes in a controllable shotgunlike manner that then triggers diverse and abundant mutations via low-fidelity repair. As a proof of principle, CARM was applied to evolve the capacity of Saccharomyces cerevisiae BY4741 to produce β-carotene. After seven rounds of iterative evolution over two months, a β-carotene hyperproducing strain, C7-143, was isolated with a 10.5-fold increase in β-carotene production and 857 diverse genomic mutations that comprised indels, duplications, inversions, and chromosomal rearrangements. Transcriptomic analysis revealed that the expression of 2541 genes of strain C7-143 was significantly altered, suggesting that the metabolic landscape of the strain was deeply reconstructed. In addition, CARM was applied to evolve industrially relevant S. cerevisiae CEN.PK2-1C for S-adenosyl-L-methionine production, which was increased 2.28 times after just one round. Thus, CARM can contribute to increasing genetic diversity to identify new phenotypes that could further be investigated by reverse engineering.

2020-12-01·BMC public health3区 · 医学

Development and evaluation of a strength-based method to promote employment of work-disability benefit recipients with multiple problems: a feasibility study

3区 · 医学

ArticleOA

作者: Brongers, Kor A ; van der Klink, Jac J L ; Cornelius, Bert ; Brouwer, Sandra

Abstract:

Background:

For people with disabilities, chances to find or keep work are negatively affected by multiple problems like lower education, poverty and poor health. Furthermore, although active labour market policies proved to be effective for unemployed in general, success rates are poor for persons who are unemployed due to multiple problems. The present study aims to describe the development of a method as well as professional training to teach its application, and to assess the feasibility of method and training. The Strength-based method (CARm) aims to promote employment of work-disability benefit recipients with multiple problems.

Methods:

The main principles of the Strength model were redesigned for better applicability in a population of work-disability beneficiaries, resulting in the CARm method. As part of the CARm method, a training module for Labour Experts (LEs) was developed. To assess the new designed method and training, a one-group, pre-post design was used. Data were collected from eight participating LEs, five female and 3 male, aged between 41and 55 years and having 2–17 years working experience. We used self-report questionnaires and a semi-structured discussion meeting after the training sessions with the LEs.

Results:

Eight labour experts (LEs) from the Dutch Social Security Institute participated in the study. Most LEs felt an improvement in their ability to ascertain developmental needs, opportunities and threats in the client’s situation. Three months after the training, LEs almost unanimously agreed on the statements ‘I expect to use the CARm method more frequently in the future’ and ‘I use the CARm method in daily practice whenever possible’. The overall rating for the training on a scale from 1 to 10 was 7.6 (range 7–9). The overall satisfaction with the trainers was good.

Conclusions:

The CARm method and training was found to be a feasible approach to facilitate LEs working at the UWV reintegration service to support clients with multiple problems. Sufficient managerial support for participating LEs is a key factor for successful implementation of CARm. Results show that CARm is worth testing for efficacy in a future trial.

项与 CT 0729 相关的新闻（医药）

2022-09-23

·生物谷

国际领先的CAR-M公司Carisma与ADC公司Sesen Bio合并，计划登录纳斯达克

以 CAR-T（嵌合抗原受体-T细胞）为代表的的癌症免疫治疗的发展，为白血病等血液类癌症带来了治愈的希望。然而一直以来，在实体瘤治疗领域，这种极具前景的治疗策略，似乎发展的并不顺利。国际领先的 CAR-M 疗法开发公司 Carisma Therapeutics 宣布与 Sesen Bio 合并，合并后的公司将以 Carisma 的名义运营，并致力于推进其用于癌症治疗的 CAR-M 细胞疗法。据悉，此次合并将在未来3-4个月内完成，届时，Carisma 将在纳斯达克上市。与此次合并的消息一起披露的还有公司新一轮融资，Carisma 获得了制药巨头艾伯维和美国默克等公司的3000万美元融资。加上此轮融资，合并后的公司将拥有约1.8亿美元的现金、等价物和有价证券，这些资金足以支持公司到2024年。 Sesen Bio 专注于治疗癌症的靶向融合蛋白疗法，其发展最快的管线是 Vicineum，这是一款抗体偶联药物（ADC），由重组人源化抗EpCAM（肿瘤细胞表面的上皮细胞粘附分子）抗体scFv与假单胞菌外毒素A偶联而成，结合癌细胞表达的EpCAM进入细胞，诱导细胞凋亡。但该 ADC 药物未获 FDA 批准上市，Sesen Bio 也停止了 Vicineum 治疗非肌肉浸润性膀胱癌（NMIBC）的3期临床试验，以保存现金流。 2017年8月，FDA 批准了诺华公司的 CAR-T 疗法上市，标志着细胞治疗时代的开启。此后 FDA 陆续批准了多款 CAR-T 疗法，用于治疗白血病、各类复发难治性淋巴瘤以及复发难治性多发性骨髓瘤领域。以 CAR-T（嵌合抗原受体-T细胞）为代表的的癌症免疫治疗的发展，为白血病等血液类癌症带来了治愈的希望。然而一直以来，在实体瘤治疗领域，这种极具前景的治疗策略，似乎发展的并不顺利。 2022年初，Carisma Therapeutics 开发的 CAR-M（嵌合抗原受体巨噬细胞）公布了1期多中心临床试验初步数据。这是首款 CAR-M 细胞疗法人体临床试验，通过基因工程改造的 CAR-M 来治疗复发性或转移性 HER2 阳性实体瘤，该1期临床试验旨在验证 CAR-M 的安全性、耐受性和可行性。宾夕法尼亚大学佩雷尔曼医学院 Saar Gill 博士开发了 CAR-M 平台，通过基因工程改造人类巨噬细胞，使其表达抗原特异性嵌合受体（例如抗HER2），从而能够靶向癌细胞上的特定抗原，并穿透实体瘤，吞噬癌细胞。此后 Saar Gill 博士等人创立了Carisma Therapeutics，旨在将 CAR-M 推向临床研究。 Saar Gill 博士表示，CAR-T 细胞被设计用于识别肿瘤特异性抗原，并在一些血液类癌症中取得了成功，但迄今为止对实体瘤还没有效果。而这项治疗实体瘤的 CAR-M 临床试验中，我们看到了输注到患者体内的巨噬细胞表现出高 CAR 表达和活性，并且耐受性良好。此外，初步数据还显示，CAR-M 具有改变实体瘤微环境以及改变骨髓细胞和 T 细胞组成的能力。 FDA 也授予了这款 CAR-M 疗法的快速通道资格，加速其对实体瘤患者的疗效和安全性的临床试验。与 CAR-T 类似的是，CAR-M 也是一种个体化细胞疗法，首先从患者血液中分离原代单核细胞，然后用所需的抗原特异性嵌合受体（例如抗HER2）对其进行修饰。由此产生的 CAR-M 细胞被冷冻保存，在需要时复苏并被输回患者体内。CAR-M 可能到达免疫学上的“冷肿瘤”，或者那些通常无法检测到或对免疫系统无反应的肿瘤，从而激活它们以帮助更容易接受治疗。仅靠肿瘤细胞难以刺激 T 细胞活化过程，但有巨噬细胞后，它们可以通过穿透实体肿瘤以引起反应，以不同的方式与肿瘤细胞接触，并且能在肿瘤内生存，这使得 CAR-M 与 CAR-T 完全不同，对于实体瘤有巨大潜力。目前，Carisma Therapeutics 共有4条 CAR-M 研究管线，靶点分别是 HER2（治疗HER2阳性实体瘤）、Mesothelin（治疗间皮素阳性实体瘤）和 PSMA（治疗转移性去势抵抗前列腺癌），以及一款体内 mRNA CAR-M 疗法。