Correction to: “Living with COVID”—implications for immunosuppressed and immunocompromised

Clinical Rheumatology -     

Mechanisms of defense in clinical ethics consultation

Medicine, Health Care and Philosophy - Clinical ethics consultants respond to a multitude of issues, ranging from the cognitive to the emotional. As such, ethics consultants must be prepared to...     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Surgical oncology during the post-COVID-19 era: What is next?

During first outburst of COVID-19, several strategies had been applied for surgical oncology patients to minimize COVID-19 transmission. COVID-19 infection seemed to compromise survival and major complication rates of surgical oncology patients. However, survival, tumor progression and recurrence rates of surgical oncology patients were associated to the consequences of COVID-19 pandemic on their management. In addition, the severity of COVID-19 infections has been downgraded. Therefore, management of surgical oncology patients should be reconsidered.     

Method’s corner: Allergist’s guide to network meta-analysis

Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.     

Evidence to Practice for Mental Health Task-Sharing: Understanding Readiness for Change among Accredited Social Health Activists in Sehore District,Madhya Pradesh,India

Involvement of community health workers (CHWs) within task-sharing to bridge the mental health treatment gap has been proven to be efficacious in randomized controlled trials. The impact of mental health programs based on task-sharing paradigm greatly depends on the performance of CHWs which, in-turn, is influenced by their readiness for change. However, there is dearth of literature assessing the role of readiness for change as an important predicator of CHW performance. The aim of this study is to examine the applicability of the readiness for change model and investigate its cultural and contextual nuances among Accredited Social Health Activists (ASHAs), a cadre of CHWs in India, to understand their engagement in mental health task-sharing. We conducted in-depth, semi-structured interviews with a purposive sample of n?=?12 key informants including ASHAs and other healthcare professionals in Sehore district, India. The interview guide consisted of open-ended questions based on the readiness for change factors including ASHAs’ attitudes towards their role in mental health care, perception of capability to implement mental health task-sharing, of support from the public health system, etc. Framework analysis with a combined inductive-deductive approach was employed to code the data and generate themes. Participants endorsed three readiness for change themes relevant to task-sharing among ASHAs including change valence or value ascribed to task-sharing, change-efficacy or the perceived ability to implement task-sharing, and job valence or value ascribed to their regular job role. In addition, they provided insights into the culturally and contextually salient aspects of these factors. Themes of personal empowerment, gaining respect and trust from community, professional duty, relationship with supervisors, and lack of resources availability were majorly highlighted. This is the first study to qualitatively investigate the applicability of the readiness for change model and its culture- and context-specific nuances among a cadre of non-specialist health workers in India. Our findings posit that implementation science models should strongly consider the culture and context within which they are being applied to enhance fit and relevance. Further, our results should be taken into consideration to adapt and validate measurement tools and build readiness for change in this population.