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.

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.

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.

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.

Spatial distribution of electrical reconnection after pulmonary vein isolation in patients with recurrent paroxysmal atrial fibrillation.

INTRODUCTION: Recurrence of atrial fibrillation after pulmonary vein isolation (PVI) occurs frequently and may be associated with electrical reconnection of the pulmonary veins (PV). We investigated spatial distribution of electrical reconnection during re-do procedures in patients with paroxysmal atrial fibrillation who had previous successful acute electrical PVI with either single irrigated tip, antral ablation (s-RF; n = 38) or multi-electrode, duty-cycled ablation (PVAC; n = 48). METHODS AND RESULTS: EP navigator, mapping and irrigated tip ablation catheters were used in all re-do procedures. Sites of reconnection were assessed in a 12-segment model. Baseline clinical and demographic characteristics were similar in both groups. The number of PVs reconnected per patient was similar in both groups (2.9 ± 0.9 and 3.2 ± 0.7 (p = 0.193), s­RF and PVAC, respectively), and each PV was equally affected. However, the inferior quadrant of the right lower PV was significantly more vulnerable to reconnection after previous PVAC ablation, whereas the superior quadrant of the right upper PV showed significantly more reconnection in the s­RF group. CONCLUSION: The overall number of PVs reconnected was equally high in both groups, and each PV was affected equally. However, there were significant differences in the spatial distribution of electrical reconnection. Better understanding of predilection sites for reconnection might help to improve the long-term success rate of PVI.

Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands.

OBJECTIVES: Selective oropharyngeal decontamination (SOD) and selective decontamination of the digestive tract (SDD) are associated with improved outcomes among patients in intensive care units (ICUs), but uncertainty remains about their long-term effects on resistance levels. We determined trends in antibiotic resistance among Gram-negative bacteria in 38 Dutch ICUs using and not using SOD/SDD. METHODS: The Infectious Disease Surveillance Information System-Antibiotic Resistance (ISIS-AR) was used to identify all Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. isolates from blood and respiratory tract specimens from ICUs between January 2008 and April 2012. Per patient, the last isolate per species per specimen per month was selected to determine cumulative resistance rates (per 100 beds/month) for colistin, tobramycin, ciprofloxacin, ceftazidime and cefotaxime/ceftriaxone in ICUs that continuously used or did not use SOD/SDD, and ICUs that introduced SOD/SDD. Time trends were analysed by multilevel Poisson regression. RESULTS: Seventeen ICUs continuously used SOD/SDD (859 months), 13 did not use SOD/SDD (663 months) and 8 introduced SOD/SDD (223 and 117 months before and after introduction). There were no discernible trends in antibiotic resistance among 637 blood isolates. For the 8353 respiratory isolates, resistance to cefotaxime/ceftriaxone increased in ICUs that did not use SOD/SDD (P < 0.001) and decreased in those that continuously used SOD/SDD (P = 0.04), as did resistance to ciprofloxacin (P < 0.001). The introduction of SOD/SDD was followed by statistically significant reductions in resistance rates for all antimicrobial agents. CONCLUSIONS: Continuous use of SOD/SDD was associated with decreasing trends for resistance to cefotaxime/ceftriaxone and ciprofloxacin. The introduction of SOD/SDD was associated with reductions in resistance rates for all antimicrobial agents included.

Targeted screening as a tool for the early detection of chronic Q fever patients after a large outbreak.

In the aftermath of the Dutch Q fever outbreak, an increasing number of patients are being diagnosed with chronic Q fever. Most of these patients are unaware of being infected with Coxiella burnetii, the causative agent of Q fever. To find patients in an earlier, asymptomatic stage, a targeted screening strategy (TSS) for patients with risk factors for chronic Q fever was started in the southeast region of Noord-Brabant. In total, 763 patients were tested using an IgG phase II indirect fluorescent antibody test (IFAT), of which 52 (7 %) patients tested positive. Ten of these 52 patients displayed a chronic Q fever serological profile. All of these 10 patients had a heart valve(s) or (endo-)vascular prosthesis. All except one were asymptomatic. Suggestive signs for chronic infections on positron emission tomography-computed tomography (PET-CT) were demonstrated in 5 (50 %) of these patients. Forty-two out of the 52 patients with a positive screening test showed a past Q fever serological profile. After a year of follow-up (every 3 months), none of these patients showed elevation of antibody titres and no new chronic Q fever patients were found in this group. A targeted screening programme is a useful instrument for detecting patients at risk of developing chronic Q fever.

The use of indicators to improve the quality of intensive care: theoretical aspects and experiences from the Dutch intensive care registry.

In the concept of total quality management that was originally developed in industry, the use of quality indicators is essential. The implementation of quality indicators in the intensive care unit to improve the quality of care is a complex process. This process can be described in seven subsequent steps of an indicator-based quality improvement (IBQI) cycle. With this IBQI cycle, a continuous quality improvement can be achieved with the use of indicator data in a benchmark setting. After the development of evidence-based indicators, a sense of urgency has to be created, registration should start, raw data must be analysed, feedback must be given, and interpretation and conclusions must be made, followed by a quality improvement plan. The last step is the implementation of changes that needs a sense of urgency, and this completes the IBQI cycle. Barriers and facilitators are found in each step. They should be identified and addressed in a multifaceted quality improvement strategy.

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.

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.

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.

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.

The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis.

BACKGROUND: Background: Different micro-organisms can be cultured from abdominal fluid obtained from patients with intra-abdominal infection resulting from a perforated digestive tract. We evaluated a cohort of patients with abdominal sepsis admitted to the intensive care with the aim of obtaining more insight into the type of microorganisms involved and the efficacy of treatment. MATERIALS AND METHODS: A 5-year prospective observational cohort study was performed in patients admitted to the intensive care unit with abdominal sepsis syndrome, defined as a perforation of the digestive tract and inflammatory response with organ failure. Abdominal fluid was obtained for microbial culture during the surgical procedures and from abdominal drains. The initial treatment protocol was cefotaxim, ciprofloxacin, metronidazole, and amphotericin B, tailored according to microbiological results. Selective decontamination of the digestive tract was administered to prevent secondary endogenous infections. RESULTS: Abdominal fluid was taken for microbial culture from 221 of the 239 patients admitted with abdominal sepsis. Aerobic Gram-negative bacteria (AGNB) were found in 52.9% of the cultures of abdominal fluid taken at the time of operation, of which 45% were Escherichia coli; in 36% of patients more than one AGNB was found. The incidence of AGNB was highest in colorectal perforations (68.6%) and perforated appendicitis (77.8%) and lowest in gastroduodenal perforations (20.5%). Gram-positive bacteria were found in 42.5% of the abdominal fluid cultures and most frequently in colorectal perforations (50.0%). Candida was found in 19.9% of patients, with 59.1% of these cultures being Candida albicans. The incidence of Candida was 41.0% in gastroduodenal perforations and 11.8% in colorectal perforation. Anaerobic bacteria were cultured in 77.8% of patients with perforated appendicitis. Over time, the prevalence of AGNB in abdominal fluid decreased from 117 patients (52.9%) in the first culture to one patient (6.7%) in week 4 (efficacy 87%). The prevalence of Gram-positive bacteria increased from 42.5% to 86.7% in a 4-week period. CONCLUSION: The composition of the intra-abdominal flora found in critically ill patients with abdominal sepsis varies depending on the location of the perforation. The efficacy of combined surgical and antibiotic treatment was 87% in 4 weeks for AGNB.

Primary prevention with the ICD in clinical practice: not as straightforward as the guidelines suggest?

At first sight, guidelines for implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death in patients with left ventricular systolic dysfunction seem unambiguous. There are clear cut-off values for ejection fraction, and functional class. However, determination of the ejection fraction itself is not unambiguous, and other risk factors for sudden death that may have a profound effect on risk are not used for decision-making. Furthermore, to obtain a clinically significant impact on survival, expected longevity is important as it can greatly compromise the benefit in elderly patients but underestimate the long-term potential of ICD therapy in younger patients. (Neth Heart J 2009;17:107-10.).

A serious complication in the puerperium: peripartum cardiomyopathy.

Two women, aged 27, presented with different symptoms shortly after giving birth to their first child. Peripartum cardiomyopathy (PPCM) was diagnosed. PPCM is a rare form of cardiac failure occurring late in pregnancy or in the postpartum period. Many women experience dyspnoea, fatigue, and pedal oedema in the last month of pregnancy or postpartum, symptoms which are identical to early congestive heart failure. Therefore, the diagnosis of PPCM requires vigilance. A high mortality rate and overall poor clinical outcome has been reported in a high percentage of these patients. Subsequent pregnancies remain controversial. (Neth Heart J 2008;16:415-8.).

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.

External validation of prognostic models for critically ill patients required substantial sample sizes.

OBJECTIVE: To investigate the behavior of predictive performance measures that are commonly used in external validation of prognostic models for outcome at intensive care units (ICUs). STUDY DESIGN AND SETTING: Four prognostic models (Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation II, and the Mortality Probability Models II) were evaluated in the Dutch National Intensive Care Evaluation registry database. For each model discrimination (AUC), accuracy (Brier score), and two calibration measures were assessed on data from 41,239 ICU admissions. This validation procedure was repeated with smaller subsamples randomly drawn from the database, and the results were compared with those obtained on the entire data set. RESULTS: Differences in performance between the models were small. The AUC and Brier score showed large variation with small samples. Standard errors of AUC values were accurate but the power to detect differences in performance was low. Calibration tests were extremely sensitive to sample size. Direct comparison of performance, without statistical analysis, was unreliable with either measure. CONCLUSION: Substantial sample sizes are required for performance assessment and model comparison in external validation. Calibration statistics and significance tests should not be used in these settings. Instead, a simple customization method to repair lack-of-fit problems is recommended.