Cantonal opioid agonist treatment authorisation systems - a mixed-method qualitative investigation.

BACKGROUND AND AIM: In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT authorisations throughout Switzerland. The primary objective was to determine how the overseeing cantonal officials implemented and perceived the legal requirements. METHOD: We started with a cross-sectional analysis of legal texts and cantonal OAT guidelines. Based on the document analysis, we conducted 26 semi-structured interviews with the cantonal officials who grant OAT authorisations. FINDINGS: In most cantons (21 of 25), the OAT authorisation is specific to the person treated and must be renewed every year. Today, 21 cantons either have implemented or are implementing the same web-based software to process and manage OAT authorisation requests. Cantons have implemented diverging requirements regarding, amongst others, the involvement of third parties in OAT and the training required of prescribing physicians. Lastly, the OAT process does not seem to be a high priority for the overseeing officials. CONCLUSIONS: From a legal standpoint, OAT authorisations should be straightforward, yet we found significant divergences among cantonal systems. We could not find scientific evidence that supports a given framework. We recommend harmonizing the 26 cantonal systems while reviewing the need for OAT authorisation.

[Therapeutic contracts and opioid agonist treatments: legally and ethically questionable]. / Contrats thérapeutiques et traitements agonistes opioïdes : juridiquement et éthiquement discutables.

In Switzerland, the use of « therapeutic contracts ¼ in the implementation of opioid agonist treatments (OAT) is frequently recommended or even imposed. These documents raise legal and ethical issues, which are presented in this article. The authors recommend that this practice be abandoned. The usual tools of medical treatments (e.g. information document, treatment plan) are sufficient.

En Suisse, l'usage de « contrats thérapeutiques ¼ dans le cadre de la mise en œuvre des traitements agonistes opioïdes (TAO) est fréquemment recommandé, voire imposé. Ces documents soulèvent des problèmes juridiques et éthiques, présentés dans cet article. Les auteurs recommandent l'abandon de cette pratique. Les outils ordinaires de la prise en charge médicale (par exemple, document d'information, plan de traitement) suffisent.

[Benzodiazepines and elderly : challenges of prescribing and deprescribing]. / Benzodiazépines et âge avancé : défis de la prescription et de la déprescription.

The elderly represent a group at risk of receiving problematic benzodiazepine (BZD) prescriptions in terms of duration or dose. The objective of this article is to investigate the difficulties related to the initial prescription, renewal, and withdrawal of BZDs in two university hospitals in French-speaking Switzerland. Specifically, we studied the actual use and perceived usefulness of clinical guidelines, the assignment of responsibilities among prescribers, and the assessment of public health risks. Eight semi-structured interviews were conducted with professionals from different specialties. A lack of usable clinical recommendations was noted, attributable to the lack of scientific knowledge and the complexity of geriatric cases. The introduction and renewal of prescriptions should be the result of systematic consultations between hospitals and ambulatory care.

Les personnes d'âge avancé représentent un groupe à risque de recevoir des prescriptions de benzodiazépines (BZD) problématiques en termes de durée ou de dose. L'objectif de cet article est d'investiguer les défis liés à la primo-prescription, la reconduction et le sevrage des BZD dans deux hôpitaux universitaires romands. Spécifiquement, nous avons étudié l'usage effectif et l'utilité perçue des recommandations cliniques, la répartition des responsabilités parmi les personnes qui prescrivent et l'appréciation des risques pour la santé publique. Huit entretiens semi-structurés ont été menés avec des professionnel-le-s de différentes spécialités hospitalières. Il est noté un manque de recommandations cliniques exploitables, s'expliquant par l'absence de connaissances scientifiques et par la complexité des cas gériatriques. L'introduction et la reconduction des prescriptions devraient faire l'objet de concertations systématiques entre les soins en hospitalier et en ambulatoire.

[Driving under the influence ]. / Conduite sous l'emprise de .

Prescribing medicines containing controlled substances (SSC : narcotics and psychotropic substances) can have legal consequences as per the Road Traffic Act. We set forth the physician's duties as well as the risks incurred by the patient. We recommend that rules regarding SSC, which can influence the capacity or the ability to drive, be clarified.

Prescrire des médicaments contenant des substances soumises à contrôle (SSC : stupéfiants et substances psychotropes) peut avoir des conséquences en matière de circulation routière. Nous présentons ici les devoirs du médecin et les risques encourus par la personne en traitement, avant de plaider pour une clarification s'agissant de médicaments pouvant influer sur la capacité ou l'aptitude à la conduite.

Switzerland's Dependence on a Diamorphine Monopoly.

In 2021, the manufacturer of diamorphine reported a possible impending shortage for Switzerland and Germany. This led us to investigate this controlled medicine's manufacture, market, and regulatory constraints. Based on our analysis of legal texts and gray literature in the form of reports and documents, we propose recommendations to prevent and address diamorphine shortages in Switzerland. Diamorphine, also known as pharmaceutical "heroin," is used medically to treat persons with severe opioid use disorder in a handful of countries. The controlled medicine is manufactured from morphine, which, in turn, is extracted from opium poppies. Studying data from the International Narcotics Control Board for 2019, we find that Switzerland accounts for almost half of the worldwide medical consumption of diamorphine. It manufactures more than half of the worldwide total and keeps the largest stocks. Moreover, Switzerland is dependent on a sole supplier of diamorphine (monopoly). As a niche product, diamorphine has an increased risk of shortage. Such a shortage would immediately threaten a valuable public health program for around 1,660 Swiss patients. We believe it is urgent to curtail the monopoly and ensure a stable supply for the future.

Switzerland's Narcotics Regulation Jungle: Off-Label Use, Counterfoil Prescriptions, and Opioid Agonist Therapy in the French-Speaking Cantons.

The word "narcotic" is often first associated with "illicit drugs". Yet, many "narcotic" and psychotropic substances are, in fact, medicines. Controlled medicines (CM) are products that meet the legal definition of both a "narcotic" under the Swiss Narcotics Act and of a medicine under the Therapeutic Products Act. We aim to examine how similar and how different, respectively, the implementation of CM regulations is throughout French-speaking Switzerland. Based on a legal analysis of the cantonal regulations, we conducted semi-structured interviews with cantonal pharmacists and cantonal physicians. We asked them how they perceive and implement the federal legal requirements. We find that some of these requirements have fallen into disuse, notably the federal duty to notify off-label use of CM. We observe that counterfoil prescriptions in their current paper format are a veritable data graveyard in the sense that they are not actively used to monitor or supervise the market. Moreover, we detect different conditions for opioid agonist treatment authorization. Some cantons require additional physicians' training or written commitments by the person treated. Our mapping of the CM regulation implementation can serve as a basis for cantons to review their practices.

The targeted delivery of interleukin-12 to the carcinoembryonic antigen increases the intratumoral density of NK and CD8+ T cell in an immunocompetent mouse model of colorectal cancer.

The recent success achieved by immune checkpoint inhibitors in the field of immuno-oncology has been less evident for the treatment of metastatic colorectal cancer (mCRC) patients. To date, cancer immunotherapy has been efficacious only in few patients bearing high mutational burden (less than 25%) mCRCs. In this Communication, we report the generation of a novel antibody cytokine fusion protein (termed Sm3E-mIL12) targeting the CRC-associated carcinoembryonic antigen (CEA). The antibody moiety bound avidly to CEA when immobilized on solid supports, and selectively stained C51 tumor cells transfected with the antigen (C51-CEA). The cytokine payload retained full activity in vitro, as compared to the parental recombinant interleukin-12 (IL12). Ex vivo microscopic analyses revealed a homogenous distribution of Sm3E-mIL12 in the neoplastic mass upon intravenous administration. In vivo, Sm3E-mIL12 was well tolerated up to 180 µg per mouse. The targeted delivery of IL12 to CEA-expressing C51 carcinomas led to durable complete responses in 60% of the treated mice. The intratumoral density of immune effector cells was markedly increased after the third injection of Sm3E-mIL12, in keeping with the progressive regression of the neoplastic mass. The data suggest that a fully human analogue may be considered for the treatment of patients with mCRC.

DNA unchained: two assays to discover and study inhibitors of the DNA clustering function of barrier-to-autointegration factor.

The protein barrier-to-autointegration factor (BAF) and its interaction partners, the LEM (LAP2B, emerin, MAN1)-domain proteins, constitute a powerful cytoplasmic DNA defense mechanism. Invading DNA molecules are quickly bound by the BAF system and trapped in membrane compartments. This decreases the nuclear uptake of DNA from the cytoplasm. Inhibition of the BAF system is therefore expected to enhance the efficacy of non-viral DNA transfection agents. In this study, we introduced a protocol for the recombinant expression of soluble BAF and developed two ELISA-type assays to discover small molecule inhibitors of BAF-dependent DNA retention by high throughput screening (HTS). The proton pump inhibitor rabeprazole as well as three compounds of the Maybridge library were identified as inhibitors of the LEM-BAF-DNA interaction chain. The inhibition was based on adduct formation with BAF cysteine residues. An enhancing effect of the compounds on cell culture transfection, however, was not observed, which may be attributed to the reducing environment of the cytoplasm that prevents the adduct formation with BAF cysteine residues. The novel assays developed here can provide new tools to further study the biological functions of the BAF system, and may lead to the identification of suitable BAF inhibitors in future HTS campaigns.