Palliative care is a multidimensional approach for patients with a life limiting, chronic and/or terminal illness. Symptom control becomes particularly important at the end of life. However, drug regimens are often very complex and prone to drug-related problems. Patient frailty and changes in physiology may influence effects and safety of a drug. Polypharmacy is highly prevalent in this population, which can lead to an increased risk of potentially inappropriate medications. This can increase risks for adverse drug reactions and interactions and significantly affect the quality of life of patients.
Alternative routes of drug administration (e.g., subcutaneous, intranasal) may be necessary, but most drugs do not have a marketing authorization for this alternative route. Therefore, off-label use (OLU) is common. To justify an OLU safety must be ensured and an effect must be evident. However, palliative care patients are usually excluded from clinical trials and data on safety and effectiveness are lacking.
In our research, we are interested in drug safety in palliative and end of life care, and how pharmacists can contribute to improve patient care. We collaborate with the Clinical Pharmacology group of the Inselspital Bern in order to provide urgently needed data on the safety and effectiveness of OLU drugs for symptom control in palliative care. Our research revolves in different settings such as hospitals, hospices and hospice-like institutions, and mobile palliative care teams.
Administration of intranasal midazolam for anxiety in palliative care – a double-blind, randomized, placebo-controlled multicenter pilot study with a nested pharmacokinetic analysis (AIM CARE study)
This double-blind, randomized, placebo-controlled parallel-group multicenter pilot study will investigate the effects and safety of different doses of intranasal MDZ for the treatment of anxiety in palliative care patients. Adult palliative care patients with self-reported acute anxiety and clinical indication for benzodiazepine treatment will receive either placebo or one of two different midazolam doses applied as unitdose intranasal spray. The primary outcome will be patient-reported levels of anxiety before and 30 minutes after study drug administration. Levels of sedation, time to first additional dose and cumulative number of additional doses for the following 24 hours will be secondary outcome parameters. In a subset of patients, basic pharmacokinetic parameters of intranasal midazolam will be assessed.
Study team: Manuel Haschke, Carla Meyer-Massetti, Ursina Wernli, Steffen Eychmüller, Caroline Hertler, Andreas Major
Funding: Internal funds, applications for external funding pending
Status: In preparation
According to international literature, off-label use (OLU) and subcutaneous (s.c.) drug administration are common in palliative care (PC). To what extent these practices are relevant in Swiss hospices has not yet been investigated. This thesis aimed to obtain an overview of the medication use in Swiss hospices and hospice-like structures to identify challenges and gaps of information related to it, with a main focus on OLU and s.c. drug administration.
The survey study in 8 Swiss hospices and hospice-like structures showed that in Swiss hospices s.c. drug administration and OLU are applied regularly. The literature revealed a total of 17 drugs for s.c. administration in PC without a marketing authorization for this route of administration (OLU) in Switzerland. A general lack of clinical guidance and evidence for these practices was identified. Pharmacists could provide clinical guidance and support clinicians by providing information materials (i.e., fact sheets).
Wernli U, Dürr F, Jean-Petit-Matile S, Kobleder A, Meyer-Massetti C. Subcutaneous Drugs and Off-label Use in Hospice and Palliative Care: A Scoping Review. J Pain Symptom Manage. 2022 Nov;64(5):e250-e259. doi: 10.1016/j.jpainsymman.2022.07.006.
Subcutaneous Drugs and Off-label Use in Hospice and Palliative Care: A Scoping Review - ScienceDirect
This thesis was a collaboration with the University of Basel.
The hospice setting is a rather new concept in Switzerland and the role of pharmacist has yet to be established. The current prescription trends remain unclear.In order to gauge how the role of pharmacists might develop in the future in the Swiss hospice settings, this master’s thesis aimed to present an overview of current prescription practices and to evaluate pharmacy services in the literature.
Important pharmacy services (i.e., deprescribing, medication reviews, and education) were identified in the literature. The retrospective medication analysis in 58 patients revealed that almost 75% of patients were treated with polypharmacy at hospice admission. The number of prescriptions in the regular drug regimen decreased steadily over time, highlighting the importance of deprescribing.
This master’s identified various pharmacists’ activities and will help to further develop the role of pharmacists in the Swiss hospice setting.
Wernli U, Hischier D, Meier CR, Jean-Petit-Matile S, Kobleder A, Meyer-Massetti C. Pharmacists' clinical roles and activities in inpatient hospice and palliative care: a scoping review. Int J Clin Pharm. 2023 Jun;45(3):577-586. doi: 10.1007/s11096-023-01535-7.
Pharmacists’ clinical roles and activities in inpatient hospice and palliative care: a scoping review - PMC (nih.gov)
Wernli U, Hischier D, Meier CR, Jean-Petit-Matile S, Panchaud A, Kobleder A, Meyer-Massetti C. Prescription Trends in Hospice Care: A Longitudinal Retrospective and Descriptive Medication Analysis. Am J Hosp Palliat Care. 2023 Aug;40(8):820-828. doi: 10.1177/10499091221130758.
Prescription Trends in Hospice Care: A Longitudinal Retrospective and Descriptive Medication Analysis - Ursina Wernli, Désirée Hischier, Christoph R. Meier, Sibylle Jean-Petit-Matile, Alice Panchaud, Andrea Kobleder, Carla Meyer-Massetti, 2023 (sagepub.com)
Complex drug regimens, as common in palliative care (PC), increase the risks for adverse drug reactions and interactions, which can significantly affect the quality of life of people with limited life expectancy. For this reason, regular and critical medication reviews should be performed and potentially inappropriate medications (PIMs) identified. The aim of this thesis was to describe prescription trends in patients receiving outpatient specialized PC and to identify criteria for PIMs in this setting.
The literature revealed describing criteria for the identification of PIMs in PC and/or the process for medication reviews in this setting. A retrospective medication analysis was performed in 75 patients receiving care by the mobile PC team Lucerne (“Brückendienst”). Polypharmacy was present in more than half of the patients in the regular drug regimen, although a decrease in number of prescribed drugs was observed from admission to specialized outpatient PC to death.
In accordance with the literature, this thesis revealed a high prevalence of polypharmacy and PIMs the outpatient specialized PC, highlighting the importance of regular medication reviews to ensure a safe and efficient drug therapy as well as to achieve a good symptom control with reduced adverse drug reactions.
This thesis was a collaboration with the University of Basel.
According to the literature, diabetes is common in palliative care (PC) patients. However, there are only very few thematically meaningful guidelines on the structured discontinuation of medication at the end of life. Uncertainties regarding the treatment strategy for type 1 (DM1) and type 2 (DM2) diabetes remain. The aim of this thesis was to investigate the drug treatment strategies and blood glucose control of DM1 and DM2 in PC, and to confirm tendencies tendencies emerging from the literature with the help of experts.
The publications included in the literature review addressed recommended blood glucose control and drug therapy adjustments in DM1 and DM2, but no consensus was found on the optimal timing of discontinuation of treatment. A survey among experts (physicians, clinical pharmacists, endocrinologists) in hospices and PC units in Switzerland revealed a lack and a need for clinical guidelines to support diabetes therapy and deprescribing in PC. Target values identified in the literature could be confirmed by the experts. This thesis revealed that there are still large information gaps, rendering clinical decisions patient individual with low guidance.
Intranasal drug administration is a promising alternative to other forms of drug administration for symptom control in palliative care (PC), due to its non-invasive, easy, and painless administration. Currently, there are only a few drugs administered intranasally in PC and most of them classify as off-label use. The main goal of this thesis was to describe the safety and tolerability of intranasal off-label/unlicensed drugs in adult patients (≥18 years) receiving PC, with a particular focus on Midazolam nasal spray (MNS).
An overview of the current published scientific research regarding intranasal drug administrations in PC was created. Subsequently, a retrospective chart review was performed, analyzing patient- and medication-related data of 63 hospitalized palliative patients at the Inselspital from 2021 to 2022, who received MNS. Although findings in the literature and the chart review revealed good tolerability, a number of clinically relevant prescription discrepancies and questionable effects were observed in the chart review, indicating a lack of standardized prescription and administration information for MNS. Based on these findings, a fact sheet for MNS was created for the staff.
This thesis was a collaboration with the University of Basel.
The prevalence of diabetes mellitus type 2 (DM2) is increasing worldwide. However, there are hardly any guidelines for deprescribing – discontinuation, dose reduction or switching to another medication - the treatment for DM2 in the context of palliative care (PC). There is an urgent need for evidence-based guidelines in order to support patients in their terminal phase of DM2 in regard to therapy deprescribing in a dignified manner. This thesis aimed to map current evidence on DM2 therapy and deprescribing in PC from the literature and to explore current practices using expert knowledge.
In the literature, 18 publications were identified, of which 13 addressed the discontinuation of DM2 therapy and 5 discussed dose reduction, drug switching, and glucose monitoring. In a subsequent survey with case-vignettes among 45 experts working in PC (physicians, clinical pharmacists), recommendations and current practices varied greatly. However, deprescribing is widely considered and recommended at the end of life, and the experts were generally open to deprescribing, including discontinuation, dose reduction or drug switching.
This thesis was a collaboration with the University of Basel.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) is common in palliative care (PC) patients, who often have multiple factors correlating with increased risk. While DVT/PE can cause distressing symptoms such as pain and dyspnea, thromboprophylaxis can increase the risk of bleeding. In current clinical practice, direct oral anticoagulants (DOACs) have gained importance as both, therapy and prophylaxis. This thesis aimed to provide a literature overview on the use of DOACs in PC, in the context of secondary prophylaxis of DVT and/or PE and of the current practice in PC institutions in Switzerland, Germany, and Austria.
Most recommendations described in the literature were based on cancer-associated thrombosis. A set of parameters to guide clinical decision-making were identified. A subsequent online survey in 41 PC experts revealed that experts showed a high readiness for the use of secondary prophylaxis of TVT/PE in PC patients and were open to consider DOACs, mainly due to a perceived high recurrence rate and symptom burden. However, a third of experts expressed difficulties in decision-making in the case of DVT/LE in end-of-life care, indicating deprescribing of DOACs in PC for primary and secondary prophylaxis as well as therapy still lacks evidence.
Medication safety and interfaces of care
Transition of care is a critical phase in healthcare management. In particular, the transition from inpatient to outpatient care is a key point for ensuring medication safety. This arises from the frequent changes in medication regimens during a hospital stay, which have the potential to cause medication-related problems (MRPs) such as dosing errors, drug-drug interactions or adherence issues.
Clinical pharmacy services are an important factor in mitigating the risk of MRPs, particularly during transition of care. Interventions to mitigate the risk of MRPs include medication reconciliation on admission and prior to discharge, medication review, i.e. the systematic and comprehensive assessment of a patient's medication to evaluate its safety, efficacy and appropriateness, or counseling patients about their medication. However, in Switzerland, as in many other European countries, clinical pharmacy services are limited. It is therefore essential to direct the limited resources of clinical pharmacy to the patients who are most likely to benefit from them.
One of the most serious consequences of MRPs in the transition from inpatient to outpatient care are medication-related readmissions (MRRs). It has been shown that a substantial amount of readmissions are medication-related and preventable. It therefore seems promising to focus clinical pharmacy resources on patients at higher risk of MRRs.
For these reasons, some of our projects focus on identifying risk factors for MRRs and appropriate clinical pharmacy services to mitigate the risk of MRRs.
We conducted a literature search of the Medline, Embase, and CINAHL databases from their start dates through May 17, 2022. We included 37 articles reporting risk factors for medication-related 30-day readmissions. The most commonly reported risk factors were polypharmacy, prescribing problems - particularly underprescribing and suboptimal drug selection - and adherence issues. The drug groups associated with the highest risk of 30-day readmission were antithrombotics, insulin, opioid analgesics and diuretics. In follow-up projects, these identified risk factors will be validated in a Delphi study and a retrospective chart review study.
Schönenberger, N., Meyer-Massetti, C. Risk factors for medication-related short-term readmissions in adults – a scoping review. BMC Health Serv Res 23, 1037 (2023).
Risk factors for medication-related short-term readmissions in adults – a scoping review | BMC Health Services Research | Full Text (biomedcentral.com)
The risk factors from the literature review were evaluated by a panel of experts consisting of clinical pharmacists, physicians and nursing experts in a Delphi study. We included a total of 31 indicators from the literature, whereof 25 were included in the final list. The indicators prioritized by the 38 experts were inadequate communication between different healthcare providers, polypharmacy (≥ 7 medications), low medication adherence rate (defined as forgetting or incorrectly administering a medication at least twice a week), complex medication regimens with ≥ 3 doses, ≥ 2 dosage forms and ≥ 2 routes of administration per day and multimorbidity (≥ 3 chronic conditions).
The indicators will determine the prioritization of patients receiving clinical pharmacy interventions upon discharge from our hospital.
Status: Finished, manuscript under consideration
Validation of risk factors for medication-related readmissions at the general internal medicine department (KAIM) of the University Hospital of Bern and development of an algorithm to automatically flag patients at high risk
The risk factors identified from the literature review and the Delphi study are validated in the Department of General Internal Medicine (KAIM) at the University Hospital Bern (Inselspital). This is done by analyzing the readmissions for their medication-relatedness and, if so, whether the readmissions could potentially have been prevented. The identified preventable medication-related readmissions are used to validate the identified risk factors from the literature and the Delphi study. The validated and applicable risk factors will then be programmed into an algorithm to flag patients at high risk of MRRs.
In following projects, these patients will undergo a clinical pharmacy discharge program.
Status: In process
Funding: Smarter medicine grant 2022
Hospital discharge is a critical point in terms of medication safety, as mediation regimens are frequently changed, necessitating a structured medication counseling for patients. In the scope of this master’s thesis, the process of medication counselling was analyzed at the Department of General Internal Medicine (KAIM) by interviewing patients and healthcare professionals. 55% of the surveyed patients wished for more information about their medications when they were discharged from hospital. As a result, a pocket card for the medication counseling process was developed and implemented at the KAIM.
The basis for many clinical pharmacist intervention is an accurate medication list. Therefore, medication reconciliation, a systematic process of comparing the patient's current medication with medical records to avoid discrepancies, is important to ensure accurate and safe medication management. In this Master’s Thesis, we developed and pilot tested a process of pharmacist-led medication reconciliation at hospital admission. We included 24 patients, taking ≥7 medications and were ≥65 years old. In these patients, we found 142 discrepancies, with the most common being that a medication was omitted (n=66, 46.5%). After this pilot test, pharmacist-led medication reconciliation was implemented into usual care at the Department of General Internal Medicine (KAIM).
In order for patients to manage their medications efficiently and competently, they need to have sufficient medication literacy. This is particularly important for patients at hospital discharge, as medication regimens are often changed during a hospital stay. As there is no widely used tool to assess medication literacy in patients at hospital discharge, we developed a first set of items to assess medication literacy by conducting a two-round Delphi study with nurses and pharmacists as experts. The 22 experts identified 27 items as relevant and measurable. The items with the highest priority related to patients’ understanding of the indication of the prescribed medications, understanding the medication plan, and timely organization and correct preparation of medications. The identified items can serve as a basis for the development of a tool to assess medication literacy.
Insufficient communication between healthcare providers was identified as one of the leading causes for medication-related problems and contributing to suboptimal patient understanding of their medication. In this Master’s Thesis, we will investigate the patient’s understanding of their medication-related information received at hospital discharge from the Department of General Internal Medicine with telephone follow-ups as well the perceived communication issues regarding medications between our hospital and other healthcare providers (pharmacies, nursing homes, home-care organizations, outpatient physicians). Based on these findings, we want to identify areas where and how clinical pharmacists could improve medication safety at hospital discharge.
Status: In process
Chronic Pain Management
Chronic non-cancer pain (CNCP) is a debilitating condition that significantly impacts physical function, emotional well-being, and relationships, often correlating with depression and insomnia. CNCP affects at least one fifth of the general population in Europe, with a higher prevalence among older individuals (28% to 88%), women, and those with lower socioeconomic backgrounds. Effectively managing CNCP poses considerable challenges. While non-pharmacological approaches such as physical or psychological therapies are typically the initial treatment choice, they may fall short in providing adequate relief. Consequently, pharmacological strategies become necessary, involving analgesics and co-analgesics like antidepressants, antiepileptics, or muscle relaxants. However, these medications carry the risk of causing medication-related problems due to adverse events or interactions with other drugs or existing health conditions. Moreover, the efficacy of these drugs is often a subject of debate, and long-term evidence is lacking.
While issues related to medication safety affect all patient groups, older individuals (aged 65 or older) face an elevated risk. Additionally, older patients tend to be more vulnerable and have a higher morbidity rate, making medication-related problems more detrimental to their overall well-being.
In our research, we strive to enhance the medication safety for older patients with CNCP. We hypothesise that clinical pharmacists, given their expertise in medications, are well positioned to address this challenge. Consequently, our goal is to develop and implement suitable clinical pharmacy services for the General Internal Medicine wards.
In this scoping review, we systematically searched Medline, Embase, PsycINFO via Ovid, the CINAHL via EBSCO databases and the Cochrane Library for articles describing pharmacist interventions in CNCP care. We included 48 studies. Pharmacist interventions varied across settings and included drug therapy optimisation (e.g. medication reconciliation, medication review), patient and healthcare provider education and therapy monitoring. Pharmacists routinely collaborated with other healthcare professions to ensure best of care. A median of 75% of reported outcome domains improved due to pharmacist interventions.
Study team: Aljoscha Goetschi, Carla Meyer-Massetti
Status: Completed, manuscript under review
Prescribing pattern insights from a longitudinal study of Older Adult Inpatients with Polypharmacy and Chronic Non-Cancer Pain
In this secondary analysis of a four-year longitudinal study of older adult inpatients with polypharmacy, we aimed to determine the prevalence of CNCP and to analyse prescription patterns. We determined a prevalence of CNCP of 9.7%. Patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics, and elevated opioid dosages. Patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid. This analysis confirmed our hypothesis that older patients with polypharmacy and CNCP are an especially vulnerable patient group that may profit from services improving their medication therapy.
Study team: Aljoscha Goetschi, Henk Verloo, Boris Wernli, Maria M. Wertli, Carla Meyer-Massetti
Status: Completed, submission pending
While we know that older patients with CNCP often suffer from medication related problems, we lack concrete guidelines to evaluate the care provided to them. Quality indicators are a suitable option to describe care provided to patients with CNCP. In an effort to develop a meaningful set of quality indicators, we are currently conducting an integrative review to consolidate current evidence. The retrieved indicators will then be validated by experts in a consensus-building Delphi-study.
Study team: Aljoscha Goetschi, Nicole Schönenberger, Ursina Wernli, Henk Verloo, Carla Meyer-Massetti
Status: Ongoing, protocol under review
This master thesis focuses on analysing facilitators and barriers for the implementation of clinical pharmacy services in the context of CNCP care. After a literature review, the identified barriers and facilitators will be discussed with healthcare professionals of the Department of General Internal Medicine (KAIM). Following these discussions, a suitable clinical pharmacy service, such as patient education at discharge, will be piloted.