Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery.

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included. A maximum of two venous plasma, target-site plasma, and target-site tissue samples were taken during surgery. The primary outcomes were the cefazolin concentrations in venous plasma, target-site plasma, and target-site tissue. A total of 27 patients [median (interquartile range) age, 42 (29-59) years; 17 (63%) male] with 138 samples were included in the study. A minimum of 6 weeks follow-up was available for all patients. The mean (SD) venous plasma, target-site plasma, and target-site tissue concentrations were 36 (13) µg/mL, 29 (13) µg/mL, and 28 (13) µg/g, respectively, and the cefazolin concentrations between the different locations of surgery did not differ significantly in both target-site plasma and target-site tissue (P = 0.822 and P = 0.840). In conclusion, 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee, significantly surpassing the MIC90 required to combat the most prevalent microorganisms. This study represents the first of its kind to assess cefazolin concentrations in the lower extremities by examining both plasma and tissue samples in this magnitude.

Using normalization process theory to evaluate the use of patient-centred outcome measures in specialist palliative home care-a qualitative interview study.

BACKGROUND: Standardised use of patient-centred outcome measures (PCOMs) improves aspects of quality of care. Normalization Process Theory (NPT) considers the social (inter-)actions of implementation processes operationalised through four constructs: coherence-building, cognitive participation, collective action and reflexive monitoring. The aim of the study was to identify barriers and enablers for the successful use of PCOMs in specialist palliative home care (SPHC) using NPT, to collect clinically meaningful and reliable data to improve patient outcomes. METHODS: Qualitative study using semi-structured interviews with palliative care professionals from German SPHC teams who participated in a study using PCOMs. Data were analysed using Framework analysis, and contextualised within NPT. RESULTS: Seventeen interviews across five teams were conducted. Some teams already had an understanding of what PCOMs are and how to use them, based on previous experience. In other teams, this understanding developed through the perception of the benefits (coherence). Participation and engagement depended on individuals and was decisive for coherence-building. The attitude of the management level also played a major role (cognitive participation). Integration of PCOMs into everyday clinical practice varied and depended on the manifestation of the first two constructs and other already established routines (collective action). In the context of appraisal, both positive (e.g. focus on patient) and negative aspects (e.g. additional work) of using PCOMs were mentioned (reflexive monitoring). CONCLUSIONS: Although benefits of using PCOMs were partly recognised, not all teams continued standardised use. Here, not only the social (inter-)actions, but also the influence of the context (working environment) were decisive. Future implementation strategies should consider integrating PCOMs in existing electronic patient records, education sessions supporting coherence-building, internal facilitators/local champions, and ensuring frequent data analyses as it is beneficial and increases the readiness of using PCOMs.

More than the sum of its parts-A constructivist grounded-theory study on specialist palliative care during crises like the COVID pandemic.

BACKGROUND: The COVID pandemic is an example of a crisis challenging healthcare systems worldwide. The impact of the pandemic on providing high-quality palliative care calls for a deeper understanding of specialist services during crises. This is essential in preparation for further crises. AIM: To develop a conceptual understanding of the impact of the pandemic on specialist palliative care as an example for arising future crises. DESIGN: Qualitative interview study across Germany, following a constructivist grounded theory methodology. SETTING/PARTICIPANTS: Eleven semi-structured interviews with experts with overarching knowledge of structures and processes in specialist palliative care between 05-07/2020 and between 02-06/2021, 23 semi-structured interviews with healthcare professionals working in a specialist palliative care setting. RESULTS: The complex system of palliative care provision during crises has properties that cannot be understood as separated parts of the care process. The pandemic led to unique structural and processual challenges characterized by interconnectedness, uncertainty, dynamic, underlying dilemmas, and unclear long-term goal. In response to the pandemic, teams experienced different phases, which enhanced adaption, innovation, and progress within complex care situations. Creative strategy approaches and dynamic responsiveness facilitated innovative development and could lead to long-lasting improvement within services. Availability of information, transparent communication, comprehensible instructions, participation in decision-making, and search for solutions contributed to teams' proactive development throughout the pandemic. CONCLUSION: Addressing the complex problems in specialist palliative care caused by crises requires system thinking and a learning mindset. This can facilitate teams to overcome the crisis and move forward rather than bounce back to normal.

Symptom and problem clusters in German specialist palliative home care - a factor analysis of non-oncological and oncological patients' symptom burden.

BACKGROUND: Specialist palliative home care (SPHC) aims to maintain and improve patients' quality of life in the community setting. Symptom burden may differ between oncological and non-oncological patients. However, little is known about diagnosis-related differences of SPHC patients. This study aims to describe the prevalence of physical symptom burden and psychosocial problems of adult patients in SPHC, and to evaluate diagnosis-related symptom clusters. METHODS: Secondary analysis of data from a prospective, cross-sectional, multi-centre study on complexity of patients, registered at the German Register for Clinical Studies (DRKS trial registration number: DRKS00020517, 12/10/2020). Descriptive statistics on physical symptom burden and psychosocial problems at the beginning of care episodes. Exploratory and confirmatory factor analyses to identify symptom and problem clusters. RESULTS: Seven hundred seventy-eight episodes from nine SPHC teams were included, average age was 75 years, mean duration of episode 18.6 days (SD 19.4). 212/778 (27.2%) had a non-oncological diagnosis. Main burden in non-oncological episodes was due to poor mobility (194/211; 91.9%) with significant diagnosis-related differences (χ² = 8.145, df = 1, p = .004; oncological: 472/562; 84.0%), and due to weakness (522/565; 92.4%) in oncological episodes. Two symptom clusters (psychosocial and physical) for non-oncological and three clusters (psychosocial, physical and communicational/practical) for oncological groups were identified. More patients in the non-oncological group compared to the oncological group showed at least one symptom cluster (83/212; 39.2% vs. 172/566; 30.4%). CONCLUSION: Patients with non-oncological diseases had shorter episode durations and were more affected by symptom clusters, whereas patients with oncological diseases showed an additional communicational/practical cluster. Our findings indicate the high relevance of care planning as an important part of SPHC to facilitate anticipatory symptom control in both groups.

Fusariosis in patients with hematological malignancies: Two case reports.

Immunosuppressed patients with hematological malignancies are at risk for invasive fungal infections (IFI), including infections with Fusarium species (spp.), which are increasingly reported. Particularly at risk are patients with acute myeloid leukemia (AML) treated with high-dose cytarabine as remission-induction therapy. Whether cytarabine increases the risk of IFI in comparison to other chemotherapy remains not fully determined. Additionally, no clear correlation between the in vitro established minimal inhibitory concentrations (MICs) of antifungal agents and clinical outcome has been established for fusariosis. To increase awareness and knowledge of invasive fusariosis, we report two cases of Fusarium spp. infections in neutropenic patients following treatment with cytarabine for AML. Despite high MICs for azoles both patients were treated with an azole in combination with liposomal amphotericin B. The combination therapy was successful in one patient, however the other patient did not survive the disseminated Fusarium infection.

Implementing ePROM in specialist palliative home care: the professionals' perspective - a mixed-methods study.

Background: Over the last decades, patient-reported outcome measures (PROM) have been developed for a better understanding of patient needs. The Integrated Palliative Care Outcome Scale (IPOS) is an internationally recommended PROM in palliative care. The validated electronic version of IPOS (eIPOS) was implemented in four German specialist palliative home care (SPHC) teams for use in everyday clinical practice. Patients reported symptoms and concerns via eIPOS, which were transmitted directly to the electronic patient record of the respective SPHC team. Objectives: The aim of the study was to describe and explore the health care professionals' (HCPs') experiences regarding acceptance and use of eIPOS in clinical practice in SPHC. Design: The mixed-methods sequential explanatory design comprised an anonymized quantitative online survey followed by qualitative focus groups. Methods: The online survey asked in both closed and open questions for HCP's experience with eIPOS. Ambiguous results from the survey were discussed in two focus groups. Survey data were analysed with descriptive and univariable statistics, and the framework approach was used for qualitative data. In a further step, we conducted integrated analysis of quantitative and qualitative results using joint displays. Results: All HCPs of the four SPHC teams (n = 52) were invited to participate. HCPs participating in the survey (n = 32) and the focus groups (n = 7) saw potentials for implementing ePROM in palliative home care - as far as it is technically easy to handle and can be easily integrated into clinical practice. Conclusion: Successful use of ePROMs is affected by the possibility of easy integration into the teams' different structures and processes and the HCPs' perceptions of potentials regarding ePROM use in SPHC. Registration: The study is registered on clinicaltrials.org (NCT03879668).

The use of electronic patient-reported outcome measures in specialist palliative home care: what do professionals think about it? A mixed-methods study Patient-reported outcome measures (PROMs) are short questionnaires developed to assess a patient's health status at a particular point in time. The Integrated Palliative Care Outcome Scale (IPOS) is such a questionnaire, and eIPOS is an electronic version of IPOS. IPOS asks about patients' symptoms and problems when they suffer from advanced diseases. We conducted this study to understand what health care professionals (HCPs) think about electronic PROMs (ePROMs) in palliative home care. We first asked the HCPs to answer questions in an online survey. Then, HCPs discussed the use of eIPOS in small discussion groups. This study design is called 'Mixed-Methods sequential design'. We found that all HCPs used the information they received through eIPOS ­ some frequently and some less often. Many HCPs see potential in using ePROMs to support care. For example, because ePROMs help them to understand patients' symptoms and problems better. However, they also pointed out that eIPOS needs technical improvement. Also, the procedures of eIPOS need to fit into the work routine of the palliative care team. The findings demonstrate the perspectives of HCPs on ePROM. These are valuable to understand how ePROM can be implemented in palliative home care. We can also learn about how to implement other digital tools in other settings of palliative care.

Accessibility to specialist palliative care services in Germany: a geographical network analysis.

BACKGROUND: The need for palliative care will increase over the next years because of the rise in deaths from chronic illness and demographic changes. The provision of specialist palliative care (SPC) in Germany (palliative care units (PCU), specialist palliative home care (SPHC) teams and palliative care advisory (PCA) teams) has been expanded in recent years. Despite the increasing availability, there is still insufficient coverage with long travel times. The aim was to describe the spatial distribution of SPC services in Germany, to calculate the potential accessibility of facilities and to assess potential spatial under-provision. METHODS: Retrospective cross-sectional study with regional analysis of SPC services in Germany. Addresses of SPC services registered online were geocoded, accessibility and network analyses were conducted, and proportion of the population living up to 60 minutes driving time were calculated. RESULTS: A total of 673 facilities were included. Their distribution is heterogeneous with every fourth of the 401 districts (110/401; 27.4%) lacking a SPC service. In half of the area of Germany the existing PCU and SPHC teams are within reach of 30 minutes, with nearly 90% of the population living there. Hospitals providing PCA teams can be reached within 30 minutes in 17% of the total area with provision for 43% of the population. CONCLUSIONS: A high coverage of SPHC teams and PCU indicates a good spatial distribution in Germany but no complete adequate provision of SPC services, especially for PCA teams. There is a persistent need for further implementation of hospital PCA teams.

Benzylpenicillin concentrations in umbilical cord blood and plasma of premature neonates following intrapartum doses for group B streptococcal prophylaxis.

BACKGROUND AND METHOD: Dutch obstetrics guideline suggest an initial maternal benzylpenicillin dose of 2,000,000 IU followed by 1,000,000 IU every 4 h for group-B-streptococci (GBS) prophylaxis. The objective of this study was to evaluate whether concentrations of benzylpenicillin reached concentrations above the minimal inhibitory concentrations (MIC) in umbilical cord blood (UCB) and neonatal plasma following the Dutch guideline. RESULTS: Forty-six neonates were included. A total of 46 UCB samples and 18 neonatal plasma samples were available for analysis. Nineteen neonates had mothers that received intrapartum benzylpenicillin. Benzylpenicillin in UCB corresponded to concentrations in plasma drawn directly postpartum (R2 = 0.88, p < 0.01). A log-linear regression suggested that benzylpenicillin concentrations in neonates remained above the MIC threshold 0.125 mg/L up to 13.0 h after the last intrapartum dose. CONCLUSIONS: Dutch intrapartum benzylpenicillin doses result in neonatal concentrations above the MIC of GBS.

Benefit of a Palliative Care Drug Information Service and User Experience: A Cross-sectional Study Using a Web-based Online Survey.

A specialized drug information service can assist professionals in collating relevant information and hereby help to increase medication safety. It is only helpful if the information provided can also be put into practice, though. The aim of this study was to evaluate the benefits of a specialized palliative care drug information service AMInfoPall and its users' experience. A web-based survey among health care professionals subsequent to inquiry between 07/2017 and 06/2018 was conducted. Twenty questions related to the use and transfer of received information into clinical practice and the result of the consecutive treatment. Invitations to participate/ reminders were sent out 8 and 11 days after receiving the requested information. The survey's response rate was 119/176 (68%). Most participants were physicians (54%), followed by pharmacists (34%) and nurses (10%), 33/119 (28%) worked in palliative home care teams, 29 (24%) on palliative care units, and 27 (23%) in retail pharmacies. 86/99 respondents had conducted an unsatisfiable literature search before contacting AMInfoPall. 113/119 (95%) were satisfied with the provided answer. Information was transferred into clinical practice as recommended in 65/119 (55%) cases and led to a change in patient status in 33%, mostly improvement. No change was reported in 31% and in 36% it was unclear. AMInfoPall was well accepted and mostly used by physicians and palliative home care services. It provided helpful support for decision-making. The obtained information was mostly well transferable into practice.

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia.

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study. A population PK model was constructed, and the probability of target attainment (PTA) was assessed during all phases of controlled TH using targets of 100% of the time that the concentration in the blood exceeds the MIC (T>MIC) (for efficacy purposes and 100% T>4×MIC and 100% T>5×MIC to prevent resistance). A total of 35 patients with 338 ceftazidime concentrations were included. An allometrically scaled one-compartment model with postnatal age and body temperature as covariates on clearance was constructed. For a typical patient receiving the current dose of 100 mg/kg of body weight/day in 2 doses and assuming a worst-case MIC of 8 mg/L for Pseudomonas aeruginosa, the PTA was 99.7% for 100% T>MIC during hypothermia (33.7°C; postnatal age [PNA] of 2 days). The PTA decreased to 87.7% for 100% T>MIC during normothermia (36.7°C; PNA of 5 days). Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised. Higher-dosing regimens (150 mg/kg/day in 3 doses during hypothermia and 200 mg/kg/day in 4 doses during normothermia) could be considered when achievements of 100% T>4×MIC and 100% T>5×MIC are desired.

The impact of the COVID-19 pandemic on processes, resource use and cost in palliative care.

BACKGROUND: The COVID-19 pandemic impacts on working routines and workload of palliative care (PC) teams but information is lacking how resource use and associated hospital costs for PC changed at patient-level during the pandemic. We aim to describe differences in patient characteristics, care processes and resource use in specialist PC (PC unit and PC advisory team) in a university hospital before and during the first pandemic year. METHODS: Retrospective, cross-sectional study using routine data of all patients cared for in a PC unit and a PC advisory team during 10-12/2019 and 10-12/2020. Data included patient characteristics (age, sex, cancer/non-cancer, symptom/problem burden using Integrated Palliative Care Outcome Scale (IPOS)), information on care episode, and labour time calculated in care minutes. Cost calculation with combined top-down bottom-up approach with hospital's cost data from 2019. Descriptive statistics and comparisons between groups using parametric and non-parametric tests. RESULTS: Inclusion of 55/76 patient episodes in 2019/2020 from the PC unit and 135/120 episodes from the PC advisory team, respectively. IPOS scores were lower in 2020 (PCU: 2.0 points; PC advisory team: 3.0 points). The number of completed assessments differed considerably between years (PCU: episode beginning 30.9%/54.0% in 2019/2020; PC advisory team: 47.4%/40.0%). Care episodes were by one day shorter in 2020 in the PC advisory team. Only slight non-significant differences were observed regarding total minutes/day and patient (PCU: 150.0/141.1 min., PC advisory team: 54.2/66.9 min.). Staff minutes showed a significant decrease in minutes spent in direct contact with relatives (PCU: 13.9/7.3 min/day in 2019/2020, PC advisory team: 5.0/3.5 min/day). Costs per patient/day decreased significantly in 2020 compared to 2019 on the PCU (1075 Euro/944 Euro for 2019/2020) and increased significantly for the PC advisory team (161 Euro/200 Euro for 2019/2020). Overhead costs accounted for more than two thirds of total costs. Direct patient cost differed only slightly (PCU: 134.7 Euro/131.1 Euro in 2019/2020, PC advisory team: 54.4 Euro/57.3 Euro). CONCLUSIONS: The pandemic partially impacted on daily work routines, especially on time spent with relatives and palliative care problem assessments. Care processes and quality of care might vary and have different outcomes during a crisis such as the COVID-19 pandemic. Direct costs per patient/day were comparable, regardless of the pandemic.

Measurement equivalence of the paper-based and electronic version of the Integrated Palliative care Outcome Scale (IPOS): A randomised crossover trial.

BACKGROUND: The Integrated Palliative Care Outcome Scale (IPOS) validly and reliably measures symptoms and concerns of those receiving palliative care. AIM: To determine the equivalence of the paper version with an electronic version of the IPOS (eIPOS). DESIGN: Multicentre randomised crossover trial (NCT03879668) with a within-subject comparison of the two modes (washout period 30 min). SETTING/PARTICIPANTS: Convenience sample of specialist inpatient and palliative home care patients aged over 18 years with cancer and non-cancer conditions was recruited. Scores were compared using intraclass correlation coefficients (ICC), Bland-Altman plots and via a mixed-effects analysis of variance. RESULTS: Fifty patients were randomised to complete paper-electronic (n = 24) and electronic-paper (n = 26) IPOS with median age 69 years (range 24-95), 56% male, 16% non-cancer. The ICCs showed very high concordance for the total score (ICC 0.99, 95% CI 0.98-1.00), lowest ICCs being observed for symptoms 'Appetite loss' and 'Drowsiness' (ICC 0.95, 95% CI 0.92-0.97). Nine of seventeen items had ICCs above 0.98, as did all subscales. No statistically significant mode, order, age, and interaction effects were observed for IPOS total score and subscales, except for 'Communication' (Fmode = 5.9, p = 0.019). Fifty-eight percent preferred the electronic version. In the group 75+ years, 53% preferred the paper version. Only three entries in the free-text main problems differed between the versions. CONCLUSION: The very high equivalence in scores and free text between the IPOS and the eIPOS demonstrates that eIPOS is feasible and reliable in an older palliative population.

Challenges developing an electronic patient-reported outcome measurement for palliative home care: A qualitative interview and focus group study.

BACKGROUND: Patient-reported outcome measures have the potential to improve outcomes, quality, and effectiveness of care. Digital use of patient-reported outcome measures could be an option to foster implementation in palliative care. The Palli-MONITOR study focused on developing and testing an electronic patient-reported outcome measure in specialised palliative home care. As part of this study, we examined setting-specific challenges for the development of the measure. AIM: We aimed to identify and explore challenges for the development of electronic patient-reported outcome measures as standardised assessment in specialised palliative home care. DESIGN: Qualitative approach with semi-structured interviews and focus groups. Data were thematically analysed using the framework method. SETTING/PARTICIPANTS: Patients and professionals from five German palliative home care teams. RESULTS: Patients described potential problems in using electronic questionnaires due to their deteriorating health. Answering the electronic questionnaire encouraged patients to reflect on their current palliative situation, which was partly perceived as burdensome. Identified concerns and questions regarding the future roll-out of electronic patient-reported outcome measurement addressed the process of receiving and using the provided information in clinical care routine. Challenging factors on organisational and structural level were the potential undermining of the established 24-h emergency call system and the potential use for patients. CONCLUSIONS: Our results provide a multifaceted picture of challenges developing electronic systems for patient-reported outcome measurement in palliative home care on the individual and organisational level. The study underpins the benefit of stakeholder involvement creating digital health innovations and emphasises the importance to therefore mind setting specific culture.

Development of a national strategy with recommendations for the care of seriously ill and dying people and their relatives in pandemics: A modified Delphi study.

BACKGROUND: The SARS-CoV-2 pandemic is a constant challenge for health care systems, also in Germany. Care of seriously ill and dying people and their relatives is often neglected and suffering increased due to sub-optimal symptom management, visiting restrictions and lonely dying. The project "Palliative Care in Pandemics (PallPan)" intended to develop a national strategy including evidence- and consensus-based recommendations for the care of seriously ill and dying people and their relatives during pandemic times in Germany. AIM: To reach consensus on evidence-based recommendations for the care of seriously ill and dying people and their relatives in pandemics. METHODS: Three-step consensus process comprising two online Delphi rounds and an expert workshop conducted from April to June 2021. One hundred twenty experts from various areas of healthcare, administration, and politics in Germany were included. RESULTS: During the consensus-process, pre-formulated evidence-based recommendations were refined step-by-step. This resulted in consensus on 33 recommendations on the topics of "supporting patients and their relatives," "supporting staff," and "supporting and maintaining structures and provision of palliative care." The recommendations address professional carers and various responsibilities on a governmental, federal state and municipal level, and in healthcare facilities. CONCLUSION: We provide evidence and consensus-based recommendations for the care of seriously ill and dying people and their relatives in pandemics in Germany. This is an important step towards a pandemic preparedness and hopefully improves the future palliative care response to pandemics.

The Impact of the SARS-CoV-2 Pandemic on the Needs of Non-Infected Patients and Their Families in Palliative Care-Interviews with Those Concerned.

During humanitarian crises, such as a pandemic, healthcare systems worldwide face unknown challenges. This study aimed to explore and describe the effect of the SARS-CoV-2 pandemic on the needs of non-infected patients and family caregivers in specialist palliative care, using qualitative, semi-structured interviews. Data were analyzed using inductive content analysis, following the framework approach. Thirty-one interviews were conducted with patients/family caregivers (15/16) in palliative care units/specialist palliative home care (21/10) from June 2020 to January 2021. Well-known needs of patients and family caregivers at the end of life remained during the pandemic. Pandemic- dependent themes were (1) implications of the risk of contagion, (2) impact of the restriction of social interactions, (3) effects on the delivery of healthcare, and (4) changes in the relative's role as family caregiver. Restriction on visits limited family caregivers' ability to be present in palliative care units. In specialist palliative home care, family caregivers were concerned about the balance between preserving social contacts at the end of life and preventing infection. Specialist palliative care during a pandemic needs to meet both the well-known needs at the end of life and additional needs in the pandemic context. In particular, attention should be given to the needs and burden of family caregivers, which became more multifaceted with regards to the pandemic.

Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review.

Gentamicin is an aminoglycoside antibiotic with a small therapeutic window that is currently used primarily as part of short-term empirical combination therapy. Gentamicin dosing schemes still need refinement, especially for subpopulations where pharmacokinetics can differ from pharmacokinetics in the general adult population: obese patients, critically ill patients, paediatric patients, neonates, elderly patients and patients on dialysis. This review summarizes the clinical pharmacokinetics of gentamicin in these patient populations and the consequences for optimal dosing of gentamicin for infections caused by Gram-negative bacteria, highlighting new insights from the last 10 years. In this period, several new population pharmacokinetic studies have focused on these subpopulations, providing insights into the typical values of the most relevant pharmacokinetic parameters, the variability of these parameters and possible explanations for this variability, although unexplained variability often remains high. Both dosing schemes and pharmacokinetic/pharmacodynamic (PK/PD) targets varied widely between these studies. A gentamicin starting dose of 7 mg/kg based on total body weight (or on adjusted body weight in obese patients) appears to be the optimal strategy for increasing the probability of target attainment (PTA) after the first administration for the most commonly used PK/PD targets in adults and children older than 1 month, including critically ill patients. However, evidence that increasing the PTA results in higher efficacy is lacking; no studies were identified that show a correlation between estimated or predicted PK/PD target attainment and clinical success. Although it is unclear if performing therapeutic drug monitoring (TDM) for optimization of the PTA is of clinical value, it is recommended in patients with highly variable pharmacokinetics, including patients from all subpopulations that are critically ill (such as elderly, children and neonates) and patients on intermittent haemodialysis. In addition, TDM for optimization of the dosing interval, targeting a trough concentration of at least < 2 mg/L but preferably < 0.5-1 mg/L, has proven to reduce nephrotoxicity and is therefore recommended in all patients receiving more than one dose of gentamicin. The usefulness of the daily area under the plasma concentration-time curve for predicting nephrotoxicity should be further investigated. Additionally, more research is needed on the optimal PK/PD targets for efficacy in the clinical situations in which gentamicin is currently used, that is, as monotherapy for urinary tract infections or as part of short-term combination therapy.

Specialist palliative care classification: typology development.

OBJECTIVES: The heterogeneity of specialist palliative care services requires a classification to enable a clear description and comparison. In Germany, specialist palliative care is provided by palliative care units, palliative care advisory teams in hospitals and palliative home care teams. The differentiation between the three care settings can serve as a first level of classification. However, due to profound variations in regulatory structures and financing systems, services within each setting are heterogeneous and characteristics remain unclear, which impedes quality management. Further characteristics of specialist palliative care models need to be considered to allow for differentiation. Thus, services should be described on a polyhierarchical basis, such as a typology, representing relevant characteristics. We aimed at the development of a comprehensive classification to facilitate the description and differentiation of specialist palliative care models. METHODS: Qualitative study including the development of a literature based, preliminary list of structural and processual characteristics, expert interviews and focus groups. Eleven interviews from May to June 2020 and two focus groups, with seven and nine participants each, in January 2021. RESULTS: Several structure and process characteristics were identified as suitable features for the specification of specialist palliative care in Germany. A classification in form of a typology including relevant characteristics has been developed. CONCLUSIONS: The advanced typology refines the existing level of differentiation within specialist palliative care services in Germany and paves the way for an improved understanding of services. This deeper insight into structure and process characteristics of specialist palliative care is necessary internationally.

COMPANION: development of a patient-centred complexity and casemix classification for adult palliative care patients based on needs and resource use - a protocol for a cross-sectional multi-centre study.

BACKGROUND: A casemix classification based on patients' needs can serve to better describe the patient group in palliative care and thus help to develop adequate future care structures and enable national benchmarking and quality control. However, in Germany, there is no such an evidence-based system to differentiate the complexity of patients' needs in palliative care. Therefore, the study aims to develop a patient-oriented, nationally applicable complexity and casemix classification for adult palliative care patients in Germany. METHODS: COMPANION is a mixed-methods study with data derived from three subprojects. Subproject 1: Prospective, cross-sectional multi-centre study collecting data on patients' needs which reflect the complexity of the respective patient situation, as well as data on resources that are required to meet these needs in specialist palliative care units, palliative care advisory teams, and specialist palliative home care. Subproject 2: Qualitative study including the development of a literature-based preliminary list of characteristics, expert interviews, and a focus group to develop a taxonomy for specialist palliative care models. Subproject 3: Multi-centre costing study based on resource data from subproject 1 and data of study centres. Data and results from the three subprojects will inform each other and form the basis for the development of the casemix classification. Ultimately, the casemix classification will be developed by applying Classification and Regression Tree (CART) analyses using patient and complexity data from subproject 1 and patient-related cost data from subproject 3. DISCUSSION: This is the first multi-centre costing study that integrates the structure and process characteristics of different palliative care settings in Germany with individual patient care. The mixed methods design and variety of included data allow for the development of a casemix classification that reflect on the complexity of the research subject. The consecutive inclusion of all patients cared for in participating study centres within the time of data collection allows for a comprehensive description of palliative care patients and their needs. A limiting factor is that data will be collected at least partly during the COVID-19 pandemic and potential impact of the pandemic on health care and the research topic cannot be excluded. TRIAL REGISTRATION: German Register for Clinical Studies trial registration number: DRKS00020517 .

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.