Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40 , 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51 , 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.     

Initial assessment of α-synuclein structure in platelets

Journal of Thrombosis and Thrombolysis - Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially...     

A commitment to marginalized children in the European Union: The hope and challenges of the EU Child Guarantee

While children in general are usually seen as a societal priority, many children are disadvantaged by marginalization, with adverse effects on health and development. Following feasibility studies, the European Commission has now adopted a formal Child Guarantee of service access. This paper links the Feasibility Studies to other reports on the need to address marginalized and institutionalized children. The problems in identifying and quantifying such children are outlined, as are the challenges of planning for these groups of children and the difficulty of finding universal definitions and data. This European Union initiative is timely, given that around a quarter of European children are marginalized, while the effects of Covid-19 will add to this marginalization.     

Evaluierung der NEF-Fehl- und Übergabeeinsätze im Raum Innsbruck

Die Anaesthesiologie - Die Qualität eines Rettungssystems zeichnet sich auch durch den effizienten Einsatz seiner personellen und Fahrzeugressourcen aus. So können im berechtigten Fall...     

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.     

Building new standards to prevent harm from medication errors in children with cancer

• Children with cancer receive many medications outside the hospital administered by their caregivers.
• The study by Walsh et al. shows the number and types of medication errors in these patients. The study includes data from three different centers.
• Importantly, the study shows the types of errors that cause harm. The authors describe how the harmful errors can be prevented.
• We suggest ways these results can be used to identify which patients and families will benefit from additional attention. Providing more help at clinic and in the home may help prevent harmful medication errors in children with cancer.

     

Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.     

Efficacy of an eConsult service to cure hepatitis C in primary care

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system. We now aim to evaluate its efficacy in curing HCV. In this retrospective cohort study, we describe rates of sustained virologic response 12 weeks after treatment completion (SVR12) for those who received primary care-based HCV treatment through the eConsult system with those who were treated in primary care independent of an eConsult from 2017 to 2019. We found there was no significant difference in the proportion of patients who achieved SVR12 between the two groups. Overall, >90% of patients who received treatment achieved SVR12. Approximately 40% of patients treated for HCV received an eConsult, suggesting utility of the eConsult in expanding access and coordinating treatment for patients within our network.