Trends in time in the management of the implantable cardioverter defibrillator in the last phase of life: a retrospective study of medical records

Background: The implantable cardioverter defibrillator (ICD) might give unwanted shocks in the last month of life. Guidelines recommend deactivation of the ICD prior to death. Aims: The aims of this study were to examine trends in time (2007–2016) in how and when decisions are made about ICD deactivation, and to examine patient- and disease-related factors which may have influenced these decisions. In addition, care and ICD shock frequency in the last month of life of ICD patients are described. Methods: Medical records of a sample of deceased patients who had their ICD implanted in 1999–2015 in a Dutch university (n = 308) or general (n = 72) hospital were examined. Results: Median age at death was 71 years, and 88% were male. ICD deactivation discussions increased from 6% for patients who had died between 2007 and 2009 to 35% for patients who had died between 2013 and 2016. ICD deactivation rates increased in these periods from 16% to 42%. Presence of do-not-resuscitate (DNR) orders increased from 9% to 46%. Palliative care consultations increased from 0% to 9%. When the ICD remained active, shocks were reported for 7% of patients in the last month of life. Predictors of ICD deactivation were the occurrence of ICD deactivation discussions after implantation (OR 69.30, CI 26.45–181.59), DNR order (OR 6.83, CI 4.19–11.12), do-notintubate order (OR 6.41, CI 3.75–10.96), and palliative care consultations (OR 8.67, CI 2.76–27.21) Conclusion: ICD deactivation discussions and deactivation rates have increased since 2007. Nevertheless, ICDs remain active in the majority of patients at the end of life, some of whom experience shocks

Implantable cardioverter defibrillator deactivation and advance care planning: A focus group study

Objective: Implantable cardioverter defibrillators can treat life-threatening arrhythmias, but may negatively influence the last phase of life if not deactivated. Advance care planning conversations can prepare patients for future decision-making about implantable cardioverter defibrillator deactivation. This study aimed at gaining insight in the experiences of patients with advance care planning conversations about implantable cardioverter defibrillator deactivation. Methods: In this qualitative study, we held five focus groups with 41 patients in total. Focus groups were audio-recorded and transcribed. Transcripts were analysed thematically, using the constant comparative method, whereby themes emerging from the data are compared with previously emerged themes. Results: Most patients could imagine deciding to have their implantable cardioverter def

Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates:A Pooled Population Pharmacokinetic Study

BACKGROUND: There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.METHODS: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used.RESULTS: The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration.CONCLUSIONS: This pooledpopulation pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.</p

Oral and intravenous amoxicillin dosing recommendations in neonates: A pooled population pharmacokinetic study

Background: There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI. Methods: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used. Results: The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks\u27 gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration. Conclusions: This pooledpopulation pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwid

Advance care planning and end-of-life care in patients with an implantable cardioverter defibrillator: The perspective of relatives

Background: Little is known about the last phase of life of patients with implantable cardioverter defibrillators and the practice of advance care planning in this population. Aim: To describe the last phase of life and advance care planning process of patients with an implantable cardioverter defibrillator, and to assess relatives’ satisfaction with treatment and care. Design: Mixed-methods study, including a survey and focus group study. Setting/participants: A survey among 170 relatives (response rate 59%) reporting about 154 deceased patients, and 5 subsequent focus groups with 23 relatives. Results: Relatives reported that 38% of patients had a conversation with a healthcare professional about implantable cardioverter defibrillator deactivation. Patients’ and relatives’ lack of knowledge about device functioning and the perceived lack of time of healthcare professionals were frequently mentioned barriers to advance care planning. Twenty-four percent of patients experienced a shock in the last month of life, which were, according to relatives, distressing for 74% of patients and 73% of relatives. Forty-two to sixty-one percent of relatives reported to be satisfied with different aspects of end-of-life care, such as the way in which wishes of the patient were respected. Quality of death was scored higher for patients with a deactivated device than those with an active device (6.74 vs 5.67 on a 10-point scale, p = 0.012). Conclusions: Implantable cardioverter defibrillator deactivation was discussed with a minority of patients. Device shocks were reported to be distressing to patients and relatives. Relatives of patients with a deactivated device reported a higher quality of death compared to relatives of patients with an active device