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Background and Objectives: There is increasing evidence that patients with dysphagia often have limited access to suitable oral dosage forms, especially when administered via an enteral feeding tube (FT). In addition, there is a lack of clear and readily available information from drug manufacturers on how to administer medications to patients with dysphagia. This study aimed to develop a practical guide for healthcare professionals to increase the safe and effective administration of oral medications to patients with dysphagia. Materials and Methods: The data were collected from existing English databases and handbooks available to develop an easy-to-use tabular guideline presenting all relevant information using keywords and short expressions. The working group differentiated 514 formulation types, and the information was collected and added to the guideline separately. In addition, the instructions for the patients taking the medicines orally or via FT were described separately. Results: The guideline consisted of 24 keywords or short expressions developed by the working group and described the instructions to use them. The guideline contained 343 active pharmaceutical ingredients and 19 fixed-dose combinations. Conclusions: Knowledge about proper medication preparation and administration for patients with swallowing difficulties is limited but essential. It is crucial to encourage drug manufacturers to provide this information as a standard to ensure the safe and effective use of medications for all patient groups.

Immune checkpoint inhibitors are increasingly used in combination with chemotherapy for the treatment of non-small cell lung cancer, yet the success of combination therapies is relatively limited. Thus, more detailed insight regarding the tumor molecular markers that may affect the responsiveness of patients to therapy is required. Here, we set out to explore the proteome of two lung adenocarcinoma cell lines (HCC-44 and A549) treated with cisplatin, pemetrexed, durvalumab, and the corresponding mixtures to establish the differences in post-treatment protein expression that can serve as markers of chemosensitivity or resistance. The mass spectrometry study showed that the addition of durvalumab to the treatment mixture resulted in cell line- and chemotherapeutic agent-dependent responses and confirmed the previously reported involvement of DNA repair machinery in the potentiation of the chemotherapy effect. Further validation using immunofluorescence also indicated that the potentiating effect of durvalumab in the case of cisplatin treatment was dependent on the tumor suppressor RB-1 in the PD-L1 weakly positive cells. In addition, we identified aldehyde dehydrogenase ALDH1A3 as the general putative resistance marker. Further studies in patient biopsy samples will be required to confirm the clinical significance of these findings.

IntroductionWhile medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice.MethodologyA semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns.ResultsThe participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy.ConclusionThe study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe.

Emergency endarterectomy of an occluded internal carotid artery (ICA) has not been investigated as an option of rescue therapy for severe acute ischemic stroke in the era of intravenous (IV) thrombolysis treatment neither as a primary treatment nor after failed IV thrombolysis. Data from the pre-IV thrombolysis era are conflicting and therefore emergency endarterectomy has not been recommended. The number of patients reaching the emergency room within the IV thrombolysis time window has vastly grown due to advanced acute stroke treatment protocols. The efficacy of mechanical thrombectomy as a primary or add-on to IV thrombolysis therapy option is being actively investigated. We herein report 2 cases of acute ischemic stroke with computerized tomography (CT) angiography-documented occlusion of an ICA that were treated with emergency carotid endarterectomy and embolectomy to restore cerebral blood flow. Both cases presented with severe stroke symptoms and signs not responding to IV thrombolysis and showed severe CT-perfusion deficits mainly representing ischemic penumbra. Blood flow was surgically restored after 5 h of symptom onset. Both patients achieved a favorable outcome. We conclude that timely surgical approach of acute ICA occlusion after failed thrombolysis as a rescue therapy may be a viable option in well-selected patients.