Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. METHODS: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. RESULTS: During a median follow-up of 28.7 months (IQR 25.2-33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. CONCLUSION: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching.

BACKGROUND: Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity. OBJECTIVES: To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis. PATIENTS AND METHODS: The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy. RESULTS: A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (ß = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (ß = 0.299; 95% CI = -0.38 to 0.98; P = 0.388). CONCLUSIONS: CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Anti-infectious decontamination strategies in Dutch intensive care units: A survey study on contemporary practice and heterogeneity.

PURPOSE: Despite increasing evidence and updated national guidelines, practice of anti-infectious strategies appears to vary in the Netherlands. This study aimed to determine the variation of current practices of anti-infectious strategies in Dutch ICUs. MATERIALS AND METHODS: In 2018 and 2019 an online survey of all Dutch ICUs was conducted with detailed questions on their anti-infectious strategies. RESULTS: 89% (63 of 71) of the Dutch ICUs responded to the online survey. The remaining ICUs were contacted by telephone. 47 (66%) of the Dutch ICUs used SDD, 14 (20%) used SOD and 10 (14%) used neither SDD nor SOD. Within these strategies considerable heterogeneity was observed in the start criteria of SDD/SOD, the regimen adjustments based on microbiological surveillance and the monitoring of the interventions. CONCLUSIONS: The proportion of Dutch ICUs applying SDD or SOD increased over time. Considerable heterogeneity in the regimens was reported. The impact of the observed differences within SDD and SOD practices on clinical outcome remains to be explored.

The development of a glucose prediction model in critically ill patients.

PURPOSE: The aim of the current study is to develop a prediction model for glucose levels applicable for all patients admitted to the ICU with an expected ICU stay of at least 24 h. This model will be incorporated in a closed-loop glucose system to continuously and automatically control glucose values. METHODS: Data from a previous single-center randomized controlled study was used. All patients received a FreeStyle Navigator II subcutaneous CGM system from Abbott during their ICU stay. The total dataset was randomly divided into a training set and a validation set. A glucose prediction model was developed based on historical glucose data. Accuracy of the prediction model was determined using the Mean Squared Difference (MSD), the Mean Absolute Difference (MAD) and a Clarke Error Grid (CEG). RESULTS: The dataset included 94 ICU patients with a total of 134,673 glucose measurements points that were used for modelling. MSD was 0.410 ± 0.495 for the model, the MAD was 5.19 ± 2.63 and in the CEG 99.8% of the data points were in the clinically acceptable regions. CONCLUSION: In this study a glucose prediction model for ICU patients is developed. This study shows that it is possible to accurately predict a patient's glucose 30 min ahead based on historical glucose data. This is the first step in the development of a closed-loop glucose system.

Prevalence of anxiety and risk associated with ventricular arrhythmia in patients with an implantable cardioverter defibrillator.

BACKGROUND: Anxiety has been associated with adverse clinical outcomes in patients who have received an implantable cardioverter defibrillator (ICD). However, results are inconclusive likely due to different measures being used to assess anxiety. Hence, the current study aims to examine the prevalence and the association between anxiety, ventricular tachyarrhythmia's (VTa's) and all-cause mortality, respectively. METHODS: Patients who received an ICD for the first time were recruited from 6 Dutch referral hospitals as part of the WEBCARE trial. Patients filled in validated questionnaires (GAD-7, STAI-S, HADS-A, ANX4, ICDC, FSAS) to assess their baseline anxiety symptomatology. Logistic regression analysis and Cox Regression analysis were performed to examine the association between anxiety with 1) VTa's and 2) mortality, respectively. RESULTS: A total of 214 Patients were included in the analysis with mean age 58.9 and 82.7% being male. The prevalence rates of anxiety varied depending on which questionnaire was used 12.4% (GAD-7), 17.5% (HADS-A), and 28.1% (STAI-S). (Cox) Regression analysis revealed that none of the anxiety measures was associated with VTa's or all-cause mortality in the current sample. Stratifying the sample by gender, the analysis showed that GAD-7, STAI-S, and ANX4 scores were associated with increased risk of VTa's but only in male patients. CONCLUSIONS: Prevalence rates of anxiety varied depending on the measurement tool used. No significant association between anxiety and VTa's and all-cause mortality was observed in the total sample. GAD-7, STAI-S, and ANX4 were associated with increased risk for VTa's but only in male patients.

Personality traits, ventricular tachyarrhythmias, and mortality in patients with an implantable cardioverter defibrillator: 6 years follow-up of the WEBCARE cohort.

OBJECTIVE: Risk stratification within the ICD population warrants the examining of the role of protective- and risk factors. Current study examines the association between Type D personality, pessimism, and optimism and risk of ventricular tachyarrhythmias (VTa's) and mortality in patients with a first-time ICD 6 years post implantation. METHODS: A total of 221 first-implant ICD patients completed questionnaires on optimism and pessimism (Life Orientation Test) and Type D personality (Type D scale DS14) 10 to 14 days after implantation. VTa's and all-cause mortality 6 years post implant comprised the study endpoints. RESULTS: Ninety (40.7%) patients had experienced VTa's and 37 (16.7%) patients died, 12 (5.4%) due to a cardiac cause. Adjusted logistic regression analysis showed that pessimism was significantly associated with increased risk of VTa's (OR = 1.09; 95% CI = 1.00-1.19; p = .05). Type D personality (OR = 1.05; 95% CI = 0.47-2.32; p = .91) and optimism (OR = 1.00; 95% CI = 0.90-1.12; p = .98) were not associated with VTa's. None of the personality types were associated with mortality. CONCLUSION: Pessimism was associated with VTa's but not with mortality. No significant association with either of the endpoints was observed for Type D personality and optimism. Future research should focus on the coexistent psychosocial factors that possibly lead to adverse cardiac prognosis in this patient population.

An alternative ICU staffing model: implementation of the non-physician provider.

INTRODUCTION: Literature in Europe regarding implementation of nurse practitioners or physician assistants in the intensive care unit (ICU) is lacking, while some available studies indicate that this concept can improve the quality of care and overcome physician shortages on ICUs. The aim of this study is to provide insight on how a Dutch ICU implemented non-physician providers (NPP), besides residents, and what this staffing model adds to the care on the ICU. METHODS: This paper defines the training course and job description of NPPs on a Dutch ICU. It describes the number and quality of invasive interventions performed by NPPs, residents, and intensivists during the years 2015 and 2016. Salary scales of NPPs and residents are provided to describe potential cost-effectiveness. RESULTS: The tasks of NPPs on the ICU are equal to those of the residents. Analysis of the invasive interventions performed by NPPs showed an incidence of central venous catheter insertion for NPPs of 20 per fulltime equivalent (FTE) and for residents 4.3 per FTE in one year. For arterial catheters the NPP inserted 61.7 per FTE and the residents inserted 11.8 per FTE. The complication rate of both groups was in line with recent literature. Regarding their salary: after five years in service an NPP earns more than a starting resident. CONCLUSION: This is the first European study which describes the role of NPPs on the ICU and shows that practical interventions normally performed by physicians can be performed with equal safety and quality by NPPs.

Accuracy and reliability of a subcutaneous continuous glucose monitoring device in critically ill patients.

Subcutaneous continuous glucose monitoring (CGM) may have benefits in achieving glycemic control in critically ill patients. The aim of this study was to assess the accuracy and reliability of the FreeStyle Navigator I in critically ill patients and to assess patient related factors influencing the accuracy and reliability. This study is a retrospective analysis of data from a randomized controlled trial conducted in a 20-bed mixed intensive care unit. Analytical accuracy, clinical accuracy and reliability were assessed against arterial blood glucose samples as reference. Assessment was according to recent consensus recommendations with median absolute relative difference (median ARD), Bland-Altman plots, the ISO system accuracy standards (ISO 15197:2013) and Clarke error grid analysis (CEG). We analyzed 2840 paired measurements from 155 critically ill patients. The median ARD of all paired values was 13.3 [6.9-22.1]%. The median ARD was significantly higher in both the hypoglycemic and the hyperglycemic range (32.4 [12.1-53.4]% and 18.7 [10.7-28.3]% respectively, p < 0.001). The Bland-Altman analysis showed a mean bias of - 0.82 mmol/L with a lower limit of agreement (LOA) of - 3.88 mmol/L and an upper LOA of 2.24 mmol/L. A total of 1626 (57.3%) values met the ISO-2013, standards and 1,334 (47%) CGM values were within 12.5% from the reference value. CEG: 71.0% zone A, 25.8% zone B, 0.5% zone C, 2.5% zone D, 0.3% zone E. The median overall real-time data display time was 94.0 ± 14.9% and in 23% of the patients, the sensor measured < 95% of the time. Additionally, data gaps longer than 30 min were found in 48% of the patients. The analytical accuracy of the FreeStyle Navigator I in critically ill patients was suboptimal. Furthermore, the clinical accuracy, did not meet the required standards. The reliability was satisfactory, however, in almost a quarter of the patients the realtime data display was < 95%. The accuracy was considerably and significantly lower in hyper- and hypoglycemic ranges.

Continuous-feed nanocasting process for the synthesis of bismuth nanowire composites.

We present a novel, continuous-feed nanocasting procedure for the synthesis of bismuth nanowire structures embedded in the pores of a mesoporous silica template. The immobilization of a bismuth salt inside the silica template from a diluted metal salt solution yields a sufficiently high loading to obtain electrically conducting bulk nanowire composite samples after reduction and sintering the nanocomposite powders. Electrical resistivity measurements of sintered bismuth nanowires embedded in the silica template reveal size-quantization effects.

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. METHODS/DESIGN: The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women. CONCLUSION: The DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.

Comparison of femoral component migration between Refobacin bone cement R and Palacos R + G in cemented total hip arthroplasty: A randomised controlled roentgen stereophotogrammetric analysis and clinical study.

AIMS: The widely used and well-proven Palacos R (a.k.a. Refobacin Palacos R) bone cement is no longer commercially available and was superseded by Refobacin bone cement R and Palacos R + G in 2005. However, the performance of these newly introduced bone cements have not been tested in a phased evidence-based manner, including roentgen stereophotogrammetric analysis (RSA). PATIENTS AND METHODS: In this blinded, randomised, clinical RSA study, the migration of the Stanmore femoral component was compared between Refobacin bone cement R and Palacos R + G in 62 consecutive total hip arthroplasties. The primary outcome measure was femoral component migration measured using RSA and secondary outcomes were Harris hip score (HHS), Hip disability and Osteoarthritis Outcome Score (HOOS), EuroQol 5D (EQ-5D) and Short Form 36 (SF-36). RESULTS: Femoral component migration was comparable between Refobacin bone cement R and Palacos R + G during the two-year follow-up period with an estimated mean difference of 0.06 mm of subsidence (p = 0.56) and 0.08° of retroversion (p = 0.82). Five hips (three Refobacin bone cement R and two Palacos R + G) showed non-stabilising, continuous migration; the femoral cement mantle in these hips, was mean 0.7 mm thicker (p = 0.02) and there were more radiolucencies at the bone-cement interface (p = 0.004) in comparison to hips showing stabilising migration. Post-operative HHS was comparable throughout the follow-up period (p = 0.62). HOOS, EQ5D, and SF-36 scores were also comparable (p-values > 0.05) at the two-year follow-up point. CONCLUSION: Refobacin bone cement R and Palacos R + G show comparable component migration and clinical outcome during the first two post-operative years. Hips showing continuous migration are at risk for early failure. However, this seems to be unrelated to cement type, but rather to cementing technique. Cite this article: Bone Joint J 2016;98-B:1333-41.

Left atrial thrombus under dabigatran in a patient with nonvalvular atrial fibrillation.

Dabigatran is a new direct competitive inhibitor of thrombin and is equally effective and safe as warfarin in the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. We present a case of a 60-year-old man with persistent nonvalvular atrial fibrillation who switched from acenocoumarol to dabigatran 110 mg twice daily. After five months the patient developed a large atrial thrombus, occlusion of the tibial arteries of the right foot, cerebellar infarction and multiple infarctions in kidneys and spleen. Blood test showed a dabigatran concentration of 35 ng/ml six hours after intake, correlating with a low trough concentration of 24-27 ng/mL and significantly increased thromboembolic risk. Other risk factors for thromboembolism were excluded. The present case indicates that in selected patients, there might be an indication for dose adjustments based on serum levels of dabigatran to ensure patient efficacy (thromboembolic events) and safety (bleeding).