HIOPP-6 - a pilot study on the evaluation of an electronic tool to assess and reduce the complexity of drug treatment considering patients' views.

BACKGROUND: A complex drug treatment might pose a barrier to safe and reliable drug administration for patients. Therefore, a novel tool automatically analyzes structured medication data for factors possibly contributing to complexity and subsequently personalizes the results by evaluating the relevance of each identified factor for the patient by means of key questions. Hence, tailor-made optimization measures can be proposed. METHODS: In this controlled, prospective, exploratory trial the tool was evaluated with nine general practitioners (GP) in three study groups: In the two intervention groups the tool was applied in a version with (GI_with) and a version without (GI_without) integrated key questions for the personalization of the analysis, while the control group (GC) did not use any tools (routine care). Four to eight weeks after application of the tool, the benefits of the optimization measures to reduce or mitigate complexity of drug treatment were evaluated from the patient perspective. RESULTS: A total of 126 patients regularly using more than five drugs could be included for analysis. GP suggested 117 optimization measures in GI_with, 83 in GI_without, and 2 in GC. Patients in GI_with were more likely to rate an optimization measure as helpful than patients in GI_without (IRR: 3.5; 95% CI: 1.2-10.3). Thereby, the number of optimization measures recommended by the GP had no significant influence (P = 0.167). CONCLUSIONS: The study suggests that an automated analysis considering patient perspectives results in more helpful optimization measures than an automated analysis alone - a result which should be further assessed in confirmatory studies. TRIAL REGISTRATION: The trial was registered retrospectively at the German Clinical Trials register under DRKS-ID DRKS00025257 (17/05/2021).

Prevalence and patient-rated relevance of complexity factors in medication regimens of community-dwelling patients with polypharmacy.

PURPOSE: To describe the prevalence of complexity factors in the medication regimens of community-dwelling patients with more than five drugs and to evaluate the relevance of these factors for individual patients. METHODS: Data were derived from the HIOPP-6 trial, a controlled study conducted in 9 general practices which evaluated an electronic tool to detect and reduce complexity of drug treatment. The prevalence of complexity factors was based on the results of the automated analysis of 139 patients' medication data. The relevance assessment was based on the patients' rating of each factor in an interview (48 patients included for analysis). RESULTS: A median of 5 (range 0-21) complexity factors per medication regimen were detected and at least one factor was observed in 131 of 139 patients. Almost half of these patients found no complexity factor in their medication regimen relevant. CONCLUSION: In most medication regimens, complexity factors could be identified automatically, yet less than 15% of factors were indeed relevant for patients as judged by themselves. When assessing complexity of medication regimens, one should especially consider factors that are both particularly frequent and often challenging for patients, such as use of inhalers or tablet splitting. TRIAL REGISTRATION: The HIOPP-6 trial was registered retrospectively on May 17, 2021, in the German Clinical Trials register under DRKS-ID DRKS00025257.

Drug Safety for Nursing-Home Residents-Findings of a Pragmatic, Cluster-Randomized, Controlled Intervention Trialin 44 Nursing Homes.

BACKGROUND: The safety of drug use by nursing-home residents can be impaired by polypharmacy, potentially inappropriate medications (PIM), and neuroleptics, as well as by a lack of adequate interprofessional coordination in the nursing home. The goal of the HIOPP-3-iTBX Trial was to improve drug safety in nursing-home residents, including a reduction of PIM and/or neu - roleptic use, by means of a complex interprofessional intervention. METHODS: This cluster-randomized, controlled trial was performed in nursing homes in Germany. Residents over age 65 were included in the trial. The intervention was carried out over six months and consisted of four elements: a drug review by trained pharmacists, educational sessions for general practitioners and nurses, a drug safety toolbox, and change management seminars for members of the three participating professions. The nursing homes in the control group continued to provide usual care. The primary endpoint was the prescription of at least one PIM and/or at least two neuroleptic drugs simultaneously. The secondary endpoints were the incidence of falls and hospitalizations, quality of life, and health-care costs. This trial is registered in the German Clinical Trials Registry (DRKS00013588). RESULTS: 44 nursing homes with 862 residents were randomized, 23 of them (with 452 residents) to the intervention group and 21 (with 410 residents) to the control group. 41% of all nursing-home residents initially took at least one PIM and/or at least two neuroleptic drugs simultaneously. Follow-up data (including, among other things, the current drug regimen) were obtained for 773 residents. The intention-to-treat analysis continued to show no difference between the intervention group and the control group with respect to the primary endpoint. CONCLUSION: This trial of an intervention to improve drug safety in nursing homes led neither to reduced prescribing of PIM and/or neuroleptic drugs, nor to any improvement in the overall health status of the nursing-home residents.

[Lessons learned: Challenges faced in the recruitment process for the cluster-randomized nursing home study HIOPP-3 iTBX]. / "Lessons learned" ­ Herausforderungen im Rekrutierungsprozess in der cluster-randomisierten Pflegeheimstudie "HIOPP-3 iTBX".

INTRODUCTION: The cluster-randomized multicenter HIOPP-3 iTBX study ('General Practitioners' Initiative to optimize Medication safety for Nursing Home Residents - using an interprofessional toolbox') aims to improve medication safety in nursing home residents through a complex interprofessional intervention focusing on neuroleptics and potentially inadequate medications. A stepwise recruitment process was used for all study participants (nursing homes, general practitioners, pharmacists, nursing home residents). The aim of this article is to describe the underlying recruitment strategy, the results of the recruitment and the measures undertaken to recruit the necessary number of participants. METHODS: The recruitment strategy and the response rates of nursing homes, general practitioners, pharmacists and nursing home residents are described. Measures to improve recruitment at the study sites and reasons for refusal to participate were documented. RESULTS: The response rate in nursing homes was 8.4 % (n=44). Of the pharmacists contacted by these nursing homes 70.3 % (n=52) participated, and 43.5 % (n=91) of all contacted general practitioners. Twenty-three (33.0 %) nursing homes had to be excluded from the study because no interprofessional team could be formed. Of all nursing home residents under the care of the participating general practitioners 862 (43,5%) persons and/or their caregivers gave consent to participate in the study. The recruitment for the study took 14 months. In the course of recruitment, recruitment strategies had to be adapted to local circumstances at the study sites. Reasons for non-participation varied between the different groups. DISCUSSION AND CONCLUSION: The main challenge in the HIOPP-3 iTBX study was to form interprofessional teams in each cluster. A stepwise, partly dependent recruitment process in a large group of potential participants presents organizational challenges that should be taken into account while planning the study. In order to reach the calculated sample size in the HIOPP-3 iTBX study, a pragmatic and flexible approach, adapted to local circumstances, was required. Further studies may benefit from the experiences made in the HIOPP-3 iTBX study.

Development of an algorithm to detect and reduce complexity of drug treatment and its technical realisation.

BACKGROUND: The increasing complexity of current drug therapies jeopardizes patient adherence. While individual needs to simplify a medication regimen vary from patient to patient, a straightforward approach to integrate the patients' perspective into decision making for complexity reduction is still lacking. We therefore aimed to develop an electronic, algorithm-based tool that analyses complexity of drug treatment and supports the assessment and consideration of patient preferences and needs regarding the reduction of complexity of drug treatment. METHODS: Complexity factors were selected based on literature and expert rating and specified for integration in the automated assessment. Subsequently, distinct key questions were phrased and allocated to each complexity factor to guide conversation with the patient and personalize the results of the automated assessment. Furthermore, each complexity factor was complemented with a potential optimisation measure to facilitate drug treatment (e.g. a patient leaflet). Complexity factors, key questions, and optimisation strategies were technically realized as tablet computer-based application, tested, and adapted iteratively until no further technical or content-related errors occurred. RESULTS: In total, 61 complexity factors referring to the dosage form, the dosage scheme, additional instructions, the patient, the product, and the process were considered relevant for inclusion in the tool; 38 of them allowed for automated detection. In total, 52 complexity factors were complemented with at least one key question for preference assessment and at least one optimisation measure. These measures included 29 recommendations for action for the health care provider (e.g. to suggest a dosage aid), 27 training videos, 44 patient leaflets, and 5 algorithms to select and suggest alternative drugs. CONCLUSIONS: Both the set-up of an algorithm and its technical realisation as computer-based app was successful. The electronic tool covers a wide range of different factors that potentially increase the complexity of drug treatment. For the majority of factors, simple key questions could be phrased to include the patients' perspective, and, even more important, for each complexity factor, specific measures to mitigate or reduce complexity could be defined.

Multidisciplinary intervention to improve medication safety in nursing home residents: protocol of a cluster randomised controlled trial (HIOPP-3-iTBX study).

BACKGROUND: Medication safety is an important health issue for nursing home residents (NHR). They usually experience polypharmacy and often take potentially inappropriate medications (PIM) and antipsychotics. This, coupled with a frail health state, makes NHR particularly vulnerable to adverse drug events (ADE). The value of systematic medication reviews and interprofessional co-operation for improving medication quality in NHR has been recognized. Yet the evidence of a positive effect on NHR' health and wellbeing is inconclusive at this stage. This study investigates the effects of pharmacists' medication reviews linked with measures to strengthen interprofessional co-operation on NHR' medication quality, health status and health care use. METHODS: Pragmatic cluster randomised controlled trial in nursing homes in four regions of Germany. A total of 760 NHR will be recruited. Inclusion: NHR aged 65 years and over with an estimated life expectancy of at least six months. Intervention with four elements: i) introduction of a pharmacist's medication review combined with a communication pathway to the prescribing general practitioners (GPs) and nursing home staff, ii) facilitation of change in the interprofessional cooperation, iii) educational training and iv) a "toolbox" to facilitate implementation in daily practice. ANALYSIS: primary outcome - proportion of residents receiving PIM and ≥ 2 antipsychotics at six months follow-up. Secondary outcomes - cognitive function, falls, quality of life, medical emergency contacts, hospital admissions, and health care costs. DISCUSSION: The trial assesses the effects of a structured interprofessional medication management for NHR in Germany. It follows the participatory action research approach and closely involves the three professional groups (nursing staff, GPs, pharmacists) engaged in the medication management. A handbook based on the experiences of the trial in nursing homes will be produced for a rollout into routine practice in Germany. TRIAL REGISTRATION: Registered in the German register of clinical studies (DRKS, study ID DRKS00013588 , primary register) and in the WHO International Clinical Trials Registry Platform (secondary register), both on 25th January 2018.

Three-dimensional hierarchical cultivation of human skin cells on bio-adaptive hybrid fibers.

The human skin comprises a complex multi-scale layered structure with hierarchical organization of different cells within the extracellular matrix (ECM). This supportive fiber-reinforced structure provides a dynamically changing microenvironment with specific topographical, mechanical and biochemical cell recognition sites to facilitate cell attachment and proliferation. Current advances in developing artificial matrices for cultivation of human cells concentrate on surface functionalizing of biocompatible materials with different biomolecules like growth factors to enhance cell attachment. However, an often neglected aspect for efficient modulation of cell-matrix interactions is posed by the mechanical characteristics of such artificial matrices. To address this issue, we fabricated biocompatible hybrid fibers simulating the complex biomechanical characteristics of native ECM in human skin. Subsequently, we analyzed interactions of such fibers with human skin cells focusing on the identification of key fiber characteristics for optimized cell-matrix interactions. We successfully identified the mediating effect of bio-adaptive elasto-plastic stiffness paired with hydrophilic surface properties as key factors for cell attachment and proliferation, thus elucidating the synergistic role of these parameters to induce cellular responses. Co-cultivation of fibroblasts and keratinocytes on such fiber mats representing the specific cells in dermis and epidermis resulted in a hierarchical organization of dermal and epidermal tissue layers. In addition, terminal differentiation of keratinocytes at the air interface was observed. These findings provide valuable new insights into cell behaviour in three-dimensional structures and cell-material interactions which can be used for rational development of bio-inspired functional materials for advanced biomedical applications.