Barriers and facilitators for therapeutic drug monitoring of beta-lactams and ciprofloxacin in the ICU: a nationwide cross-sectional study.

BACKGROUND: Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited. Therefore, perceived barriers and facilitators are important for implementing TDM in this population. The primary aim of this study was to identify healthcare professionals' barriers and facilitators for the implementation of TDM of beta-lactams and ciprofloxacin in Dutch intensive care units (ICU). METHODS: We conducted a nationwide cross-sectional online survey among healthcare professionals (HCPs) involved in antibiotic treatment of ICU patients. An adapted version of the Measurement Instrument for Determinants of Innovations was sent out. Items were considered barriers when ≥ 20% of participants responded with a negative answer. If ≥ 80% of the participants responded with a positive answer, the item was considered a facilitator. RESULTS: Sixty-four HCPs completed the survey, of which 14 were from academic hospitals, 25 from general hospitals, and 25 from teaching hospitals. Most participants were hospital pharmacists (59%) or medical specialists (23%). Eleven barriers and four facilitators for implementation of TDM of beta-lactams were identified; 17 barriers for TDM of ciprofloxacin and no facilitators. The most important barriers were a lack of conclusive evidence, organizational support, and low availability of assays. Additional barriers were a lack of consensus on which specific patients to apply TDM and which pharmacodynamic targets to use. Identified facilitators for beta-lactam TDM implementation are low complexity and high task perception, combined with the perception that TDM is important to prevent side effects and to adequately treat infections. Twenty-eight percent of participants reported that flucloxacillin could be analyzed in their hospital. Assay availability of other beta-lactams and ciprofloxacin was lower (3-17%). CONCLUSION: Several barriers were identified that could obstruct the implementation of TDM of beta-lactams and ciprofloxacin in the ICU. In particular, education, clear guidelines, and organizational support should be considered when creating tailored implementation strategies. Finally, evidence of beneficial clinical outcomes on TDM of beta-lactams and ciprofloxacin can enhance further implementation.

Advance care planning in patients with advanced cancer: A 6-country, cluster-randomised clinical trial.

BACKGROUND: Advance care planning (ACP) supports individuals to define, discuss, and record goals and preferences for future medical treatment and care. Despite being internationally recommended, randomised clinical trials of ACP in patients with advanced cancer are scarce. METHODS AND FINDINGS: To test the implementation of ACP in patients with advanced cancer, we conducted a cluster-randomised trial in 23 hospitals across Belgium, Denmark, Italy, Netherlands, Slovenia, and United Kingdom in 2015-2018. Patients with advanced lung (stage III/IV) or colorectal (stage IV) cancer, WHO performance status 0-3, and at least 3 months life expectancy were eligible. The ACTION Respecting Choices ACP intervention as offered to patients in the intervention arm included scripted ACP conversations between patients, family members, and certified facilitators; standardised leaflets; and standardised advance directives. Control patients received care as usual. Main outcome measures were quality of life (operationalised as European Organisation for Research and Treatment of Cancer [EORTC] emotional functioning) and symptoms. Secondary outcomes were coping, patient satisfaction, shared decision-making, patient involvement in decision-making, inclusion of advance directives (ADs) in hospital files, and use of hospital care. In all, 1,117 patients were included (442 intervention; 675 control), and 809 (72%) completed the 12-week questionnaire. Patients' age ranged from 18 to 91 years, with a mean of 66; 39% were female. The mean number of ACP conversations per patient was 1.3. Fidelity was 86%. Sixteen percent of patients found ACP conversations distressing. Mean change in patients' quality of life did not differ between intervention and control groups (T-score -1.8 versus -0.8, p = 0.59), nor did changes in symptoms, coping, patient satisfaction, and shared decision-making. Specialist palliative care (37% versus 27%, p = 0.002) and AD inclusion in hospital files (10% versus 3%, p < 0.001) were more likely in the intervention group. A key limitation of the study is that recruitment rates were lower in intervention than in control hospitals. CONCLUSIONS: Our results show that quality of life effects were not different between patients who had ACP conversations and those who received usual care. The increased use of specialist palliative care and AD inclusion in hospital files of intervention patients is meaningful and requires further study. Our findings suggest that alternative approaches to support patient-centred end-of-life care in this population are needed. TRIAL REGISTRATION: ISRCTN registry ISRCTN63110516.

Mobile Health Coaching on Nutrition and Lifestyle Behaviors for Subfertile Couples Using the Smarter Pregnancy Program: Model-Based Cost-Effectiveness Analysis.

BACKGROUND: The health care costs for reproductive care have substantially increased with the use of in vitro fertilization (IVF) treatment. The mobile health (mHealth) coaching program Smarter Pregnancy is an effective intervention to improve nutrition and lifestyle behaviors and pregnancy rates in (sub)fertile couples, including those who undergo IVF treatment. Therefore, we hypothesize that this mHealth program can also reduce health care costs associated with IVF treatment. OBJECTIVE: This study aimed to evaluate the cost-effectiveness of the mHealth coaching program Smarter Pregnancy and compare it to usual care in women of subfertile couples who start their first IVF cycle. METHODS: This model-based cost-effectiveness analysis was performed on data from couples undergoing IVF treatment at the Erasmus MC, University Medical Center Rotterdam. A decision tree model was used to assess the incremental cost-effectiveness ratio (ICER) of ongoing pregnancies and costs of use of the mHealth program as compared to usual care. A probabilistic sensitivity analysis was performed to consider the uncertainty surrounding the point estimates of the input parameters. RESULTS: Based on our model including 793 subfertile women undergoing IVF treatment, use of the mHealth program resulted in 86 additional pregnancies and saved €270,000 compared to usual care after two IVF cycles, with an ICER of -€3050 (95% CI -3960 to -540) per additional pregnancy. The largest cost saving was caused by the avoided IVF treatment costs. Sensitivity analyses showed that the mHealth program needs to increase the ongoing pregnancy rate by at least 51% after two IVF cycles for cost saving. CONCLUSIONS: The mHealth coaching program Smarter Pregnancy is potentially cost saving for subfertile couples preceding their first IVF treatment. Implementation of this mHealth program in routine preconception care for subfertile couples should be seriously considered, given the relatively low costs and promising cost-effectiveness estimates.

Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit: A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.