Question-based development of high-risk medical devices: A proposal for a structured design and review process.

INTRODUCTION: The recent introduction of the European Medical Device Regulation poses stricter legislation for manufacturers developing medical devices in the EU. Many devices have been placed into a higher risk category, thus requiring more data before market approval, and a much larger focus has been placed on safety. For implantable and Class III devices, the highest risk class, clinical evidence is a necessity. However, the requirements of clinical study design and developmental outcomes are only described in general terms due to the diversity of devices. METHODS: A structured approach to determining the requirements for the clinical development of high-risk medical devices is introduced, utilizing the question-based development framework, which is already used for pharmaceutical drug development. An example of a novel implantable device for haemodialysis demonstrates how to set up a relevant target product profile defining the device requirements and criteria. The framework can be used in the medical device design phase to define specific questions to be answered during the ensuing clinical development, based upon five general questions, specified by the question-based framework. RESULTS: The result is a clear and evaluable overview of requirements and methodologies to verify and track these requirements in the clinical development phase. Development organizations will be guided to the optimal route, also to abandon projects destined for failure early on to minimize development risks. CONCLUSION: The framework could facilitate communication with funding agencies, regulators and clinicians, while highlighting remaining 'known unknowns' that require answering in the post-market phase after sufficient benefit is established relative to the risks.

Doctors' alertness, contentedness and calmness before and after night shifts: a latent profile analysis.

BACKGROUND: While night shifts are crucial for patient care, they threaten doctors' well-being and performance. Knowledge of how the impact of night shifts differs for doctors is needed to attenuate the adverse effects of night shifts. This study aimed to obtain more precise insight into doctors' feelings surrounding night shift by: identifying profiles based on doctors' alertness, contentedness and calmness scores before and after night shifts (research question (RQ) 1); assessing how doctors' pre- and post-shift profiles change (RQ2); and determining associations of doctors' demographics and shift circumstances with alertness, contentedness and calmness change (RQ3). METHODS: Latent Profile Analysis using doctors' pre- and post-shift self-rated alertness, contentedness and calmness scores was employed to identify pre- and post-shift profiles (RQ1). A cross-tabulation revealed pre- and post-shift profile changes (RQ2). Multiple regressions determined associations of demographics (i.e. age, sex, specialty) and night shift circumstances (i.e. hours worked pre-call, hours awake pre-call, shift duration, number of consecutive shifts, total hours of sleep) with alertness, contentedness and calmness change (RQ3). RESULTS: In total, 211 doctors participated with a mean age of 39.8 ± 10 years; 47.4% was male. The participants included consultants (46.4%) and trainees (53.6%) of the specialties surgery (64.5%) and obstetrics/gynaecology (35.5%). Three pre-shift (Indifferent, Ready, Engaged) and four post-shift profiles (Lethargic, Tired but satisfied, Excited, Mindful) were found. Most doctors changed from Ready to Tired but satisfied, with alertness reducing most. Age, specialty, sleep, shift duration and the number of consecutive shifts associated with alertness, contentedness and calmness changes. CONCLUSIONS: The results provided nuanced insight into doctors' feelings before and after night shifts. Future research may assess whether specific subgroups benefit from tailored interventions.

High on-treatment platelet reactivity in peripheral arterial disease: A systematic review.

OBJECTIVES: To highlight current evidence pertaining to the measurement methods and prevalence of high on-treatment platelet reactivity (HTPR) in patients with PAD, as well as to evaluate the relationship between HTPR and recurrent adverse cardiovascular and limb events in PAD patients. METHODS: A systematic review of English-language literature on HTPR in patients with PAD. An electronic literature search of PubMed and Medline was performed in May 2021. RESULTS: A total of 29 studies with a total number of 11,201 patients with PAD were identified. HTPR during clopidogrel treatment ranges from 9.8 to 77%, and during aspirin treatment ranges from 4.1 to 50% of PAD patients. HTPR was associated with adverse clinical outcomes. The need for limb revascularisation was higher in patients with HTPR during clopidogrel use. Similarly, HTPR during aspirin use in the PAD population was predictive of adverse cardiovascular events (HR 3.73; 95% CI, 1.43-9.81; p = .007). A wide range of techniques were applied to measure platelet resistance, without consensus on cut-off values. Furthermore, differing patient populations, a variety of antiplatelet regimens, and differing clinical endpoints highlight the high degree of heterogeneity in the studies included in this review. CONCLUSION: No consensus on technique or cut-off values for HTPR testing has been reached. Patients with HTPR are potentially at a greater risk of adverse limb-related and cardiovascular events than patients sensitive to antiplatelet therapy illustrating the need for clinical implementation of HTPR testing. Future research must aim for consistent methodology. Adaptation of antiplatelet therapy based on HTPR results requires further exploration.

Assessment of fitness to perform using a validated self-test in obstetric and gynecological night shifts in the Netherlands.

BACKGROUND: The field of obstetrics and gynecology requires complex decision-making and skills because of unexpected high-risk situations. These skills are influenced by alertness, reaction time, and concentration. Night shifts result in sleep deprivation, which might impair these functions, although it is still unclear to what extent. OBJECTIVE: This study aimed to investigate whether a night shift routinely impairs the obstetrics and gynecology consultants' and residents' fitness to perform and whether this reaches a critical limit compared with relevant frames of reference. STUDY DESIGN: Residents (n=33) and consultants (n=46) in obstetrics and gynecology conducted multiple measurements (n=415) at precall, postcall, and noncall moments with the fitness to perform self-test. The self-test consists of an adaptive pursuit tracking task that is able to objectively measure alertness, reaction time, concentration, and hand-eye coordination and Visual Analog Scale tests to subjectively score alertness. The test is validated with a sociolegal reference of a 0.06% ethanol blood concentration (the peak level after 2 units of alcohol, the legal driving limit). This equals -1.37% on the objective score and -8.17 points on subjective alertness. Linear mixed models were used to analyze the difference within subjects over a night shift, integrating repeated measures over time. RESULTS: The overnight objective difference between postcall and precall measurements was -0.62 (P<.05) for residents and 0.28 (P=NS) for consultants, both not exceeding the sociolegal reference as a group. Objective impairment exceeded the reference for 31% of the residents and 28% of the consultants. Subjective alertness decreased in residents (-18.26; P<.001) and consultants (-10.85; P<.001), both exceeding the reference. No residents had to continue work postcall versus 7.8% of the consultants. None of the consultants that had to continue work were in an objective critically impaired state. CONCLUSION: This study provides insight and awareness of individual performance after night shifts with clear frames of reference. The performance of residents is negatively and significantly affected by night shifts; therefore, a scheduled day off after a night shift is justified. Consultants showed no overall impairment; however, a quarter did exceed the alcohol limit reference after their night shift. If not logistically feasible to schedule a protected day off after a night shift, our group recommends safe shift scheduling, including options to transfer care after a demanding night shift to prevent working in a compromised state.

Stent Graft Sizing for Endovascular Abdominal Aneurysm Repair Using Open Source Image Processing Software.

INTRODUCTION: An important step to reach a favorable outcome of abdominal endovascular aneurysm repair (EVAR) is preoperative sizing of the stent graft using computed tomography angiography (CTA) images of the abdominal aorta. A variety of costly image processing software options is available to obtain the necessary aortic measurements. A package that can be used for EVAR sizing is OsiriX Lite®-an open source, freely downloadable image processing option. This study assesses the concurrent validity of OsiriX Lite® when compared with commercially available 3Mensio Vascular® and Siemens Syngo.via®. METHODS: CTA scans of 20 patients that underwent EVAR for abdominal aneurysm were selected, 10 elective and 10 ruptured. For each scan, 6 observers determined 20 parameters needed for proper stent graft sizing, 2 using Osirix Lite®, 3 using 3Mensio Vascular®, and 1 using Siemens Syngo.via®. For each parameter, an intraclass correlation coefficient (ICC) and a P-value were calculated. Interrater agreement was interpreted using the Koo and Li Guidelines. Time needed to perform EVAR planning was compared. RESULTS: Overall interrater agreement between the 3 sizing options was found to be either "good" or "moderate" for 16 out of 20 parameters (80%). Time needed to perform EVAR planning was not significantly different for Osirix Lite® (568 sec) when compared with 3Mensio Vascular® (603 sec) or Siemens Syngo.via® (659 sec) with a P-value of 0.88. CONCLUSIONS: The authors conclude that Osirix Lite® is an accurate and time-effective image processing option for preoperative sizing of an EVAR stent graft when matched to 3Mensio Vascular® and Siemens Syngo.via®.

Objective Assessment of Fitness to Perform (FTOP) After Surgical Night Shifts in the Netherlands: An Observational Study Using the Validated FTOP Self-test in Daily Surgical Practice.

BACKGROUND: Surgical skills and decision making are influenced by alertness, reaction time, eye-hand coordination, and concentration. Night shift might impair these functions but it is unclear to what extent. The aim of this study was to investigate whether a night shift routinely impairs the surgeon's fitness to perform and whether this reaches a critical limit as compared to relevant frames of reference. METHODS: Consultants (n = 59) and residents (n = 103) conducted fitness to perform measurements at precall, postcall, and noncall moments. This validated self-test consists of an adaptive tracker that is able to objectively measure alertness, reaction time, concentration, and eye-hand coordination, and multiple visual analog scales to subjectively score alertness. Results are compared to sociolegal (ethanol) and professional (operative skills) frames of reference that refer to a decrease under the influence of 0.06% ethanol. RESULTS: Residents spent 1.7 call hours asleep on average as compared to 5.4 for consultants. Subjective alertness decreased in residents after night shifts (-13, P < 0.001) but not in consultants (-1.2, P = NS). The overnight difference in tracker score was -1.17 (P < 0.001) for residents and 0.46 (P = NS) for surgeons. Postcall subjective alertness only correlated to objective alertness in consultants. For residents, hours slept on-call correlated to objective alertness. For consultants, subsequent night calls significantly correlated to objective alertness, with the third subsequent call related to performance below the reference. CONCLUSIONS: Consultants remain fit to perform after night call, but subsequent calls may compromise clinical activities. This study provides insight and awareness of individual performance with clear frames of reference.

A systematic review of the use of near-infrared fluorescence imaging in patients with peripheral artery disease.

OBJECTIVE: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe media sclerosis. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) can provide information about tissue perfusion and has already been studied in oncologic, reconstructive, and cardiac surgery. For patients with PAD, this technique might give insight into skin perfusion and thereby guide treatment. We performed a systematic review of the literature on the use of NIR fluorescence imaging in patients with PAD. METHODS: PubMed, MEDLINE, Embase, and Cochrane were searched for articles and abstracts on the application of NIR fluorescence imaging using ICG as fluorescent dye in patients with PAD. Our search strategy combined the terms "fluorescence," "ICG," or synonyms and "peripheral artery disease" or synonyms. The extracted data included fluorescence parameters and test characteristics for diagnosis of PAD. RESULTS: Twenty-three articles were found eligible for this review using 18 different parameters for evaluation of the fluorescence signal intensity. NIR fluorescence imaging was used for four main indications: diagnosis, quality control in revascularization, guidance in amputation surgery, and visualization of vascular structures. For the diagnosis of PAD, NIR fluorescence imaging yields a sensitivity ranging from 67% to 100% and a specificity varying between 72% and 100%. Significant increases in multiple fluorescence parameters were found in comparing patients before and after revascularization. CONCLUSIONS: NIR fluorescence imaging can be used for several indications in patients with PAD. NIR fluorescence imaging seems promising in diagnosis of PAD and guidance of surgeons in treatment, especially in patients in whom current diagnostic methods are not applicable. Further standardization is needed to reliably use this modality in patients with PAD.

Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas.

The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout ( Rxfp1-/-) on AVF maturation in a murine model of AVF failure. Rxfp1-/- mice showed a 22% decrease in vessel size at the venous outflow tract 14 d after AVF surgery. Furthermore, a 43% increase in elastin content was observed in the lesions of Rxfp1-/- mice and coincided with a 41% reduction in elastase activity. In addition, Rxfp1-/- mice displayed a 6-fold increase in CD45+ leukocytes, along with a 2-fold increase in monocyte chemoattractant protein 1 (MCP1) levels, when compared with wild-type mice. In vitro, VSMCs from Rxfp1-/- mice exhibited a synthetic phenotype, as illustrated by augmentation of collagen, fibronectin, TGF-ß, and platelet-derived growth factor mRNA. In addition, VSMCs derived from Rxfp1-/- mice showed a 5-fold increase in cell migration. Finally, RXFP1 and RLN expression levels were increased in human AVFs when compared with unoperated cephalic veins. In conclusion, RXFP1 deficiency hampers elastin degradation and results in induced vascular inflammation after AVF surgery. These processes impair OR in murine AVF, suggesting that the RLN axis could be a potential therapeutic target for promoting AVF maturation.-Bezhaeva, T., de Vries, M. R., Geelhoed, W. J., van der Veer, E. P., Versteeg, S., van Alem, C. M. A., Voorzaat, B. M., Eijkelkamp, N., van der Bogt, K. E., Agoulnik, A. I., van Zonneveld, A.-J., Quax, P. H. A., Rotmans, J. I. Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas.

Arteriovenous Fistula Maturation Failure in a Large Cohort of Hemodialysis Patients in the Netherlands.

OBJECTIVES: Radiocephalic arteriovenous fistulas (RCAVF) are the preferred vascular access (VA) for hemodialysis (HD). Cohort studies from North America revealed that nonmaturation is a significant disadvantage of RCAVFs compared to other VAs. DESIGN: This present retrospective study describes the incidence of nonmaturation of AVFs and functional failure of arteriovenous grafts (AVG) in a multicentre cohort in the Netherlands and attempts to create a prediction model for nonmaturation of RCAVFs. Furthermore, the efficacy of interventions to promote maturation as well as the variability between hemodialysis centers was evaluated. MATERIALS: Medical records from 8 hospitals from 1997 to 2016 were retrospectively evaluated for VA type, maturation/primary success and demographics and comorbidities. METHODS: A prediction model was created for RCAVF nonmaturation using multivariate logistic regression analysis, selecting significant predictors using backward selection. Discrimination and calibration of the model were assessed. RESULTS: 1383 AVFs and 273 AVGs were included in 1221 patients. Overall nonmaturation was 24% for RCAVFs, and 11% for upper arm AVFs. The functional failure rate for AVGs was 6%. The nonmaturation rate of contralateral RCAVFs after failure of an RCAVF was 22%. Procedures to improve RCAVF maturation were successful in 98/142 cases (69%). Predictors for nonmaturation were female gender, peripheral vascular disease, cerebrovascular disease and a cephalic vein diameter <2.5 mm, but the prediction model lacked sensitivity and specificity predicting individual RCAVF nonmaturation (C-statistic 0.629). CONCLUSION: Nonmaturation rates are highest for RCAVFs, but nonmaturation could not be predicted with demographic parameters.

An implantable magnetic drive mechanism for non-invasive arteriovenous conduit blood flow control.

OBJECTIVE: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions. METHODS: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses. RESULTS: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9±4.2 N, 46.7±1.9 N, 25.6±0.7 N, 13.5±0.6 N and 6.3±0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm. CONCLUSION: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects. SIGNIFICANCE: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Near-Infrared Fluorescence Imaging With Indocyanine Green to Predict Clinical Outcome After Revascularization in Lower Extremity Arterial Disease.

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P-values <.001), while no significant differences were seen in the group without clinical improvement (P-values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P-values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients.

Optimising Access Surgery in Senior Haemodialysis Patients (OASIS): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Current evidence on vascular access strategies for haemodialysis patients is based on observational studies that are at high risk of selection bias. For elderly patients, autologous arteriovenous fistulas that are typically created in usual care may not be the best option because a significant proportion of fistulas either fail to mature or remain unused. In addition, long-term complications associated with arteriovenous grafts and central venous catheters may be less relevant when considering the limited life expectancy of these patients. Therefore, we designed the Optimising Access Surgery in Senior Haemodialysis Patients (OASIS) trial to determine the best strategy for vascular access creation in elderly haemodialysis patients. METHODS AND ANALYSIS: OASIS is a multicentre randomised controlled trial with an equal participant allocation in three treatment arms. Patients aged 70 years or older who are expected to initiate haemodialysis treatment in the next 6 months or who have started haemodialysis urgently with a catheter will be enrolled. To detect and exclude patients with an unusually long life expectancy, we will use a previously published mortality prediction model after external validation. Participants allocated to the usual care arm will be treated according to current guidelines on vascular access creation and will undergo fistula creation. Participants allocated to one of the two intervention arms will undergo graft placement or catheter insertion. The primary outcome is the number of access-related interventions required for each patient-year of haemodialysis treatment. We will enrol 195 patients to have sufficient statistical power to detect an absolute decrease of 0.80 interventions per year. ETHICS AND DISSEMINATION: Because of clinical equipoise, we believe it is justified to randomly allocate elderly patients to the different vascular access strategies. The study was approved by an accredited medical ethics review committee. The results will be disseminated through peer-reviewed publications and will be implemented in clinical practice guidelines. TRIAL REGISTRATION NUMBER: NL7933. PROTOCOL VERSION AND DATE: V.5, 25 February 2021.

Outcomes after kidney transplantation, let's focus on the patients' perspectives.

Graft function and patient survival are traditionally the most used parameters to assess the objective benefits of kidney transplantation. Monitoring graft function, along with therapeutic drug concentrations and transplant complications, comprises the essence of outpatient management in kidney transplant recipients (KTRs). However, the patient's perspective is not always included in this process. Patients' perspectives on their health after kidney transplantation, albeit subjective, are increasingly acknowledged as valuable healthcare outcomes and should be considered in order to provide patient-centred healthcare. Such outcomes are known as patient-reported outcomes (PROs; e.g. health-related quality of life and symptom burden) and are captured using PRO measures (PROMs). So far, PROMs have not been routinely used in clinical care for KTRs. In this review we will introduce PROMs and their potential application and value in the field of kidney transplantation, describe commonly used PROMs in KTRs and discuss structural PROMs implementation into kidney transplantation care.

Perfusion Parameters in Near-Infrared Fluorescence Imaging with Indocyanine Green: A Systematic Review of the Literature.

(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.

Patency Outcomes of Arteriovenous Fistulas and Grafts for Hemodialysis Access: A Trade-Off between Nonmaturation and Long-Term Complications.

Background: Arteriovenous fistulas (AVFs) for hemodialysis (HD) are often associated with better outcomes than arteriovenous grafts (AVGs). We aimed to investigate vascular access (VA) outcomes and assessed if AVF nonmaturation outweighs long-term complications of AVGs. Methods: In this multicenter, retrospective cohort study in The Netherlands, 1- and 3-year primary, primary assisted, secondary, and functional patency rates were calculated, and the incidence of adverse events and procedures was assessed. Functional patency of RCAVFs, upper arm AVFs, and AVGs was compared using Cox analyses. Results: In total, 1041 patients who received their first VA were included, of whom 863 had VAs that successfully matured. These patients were analyzed with a median follow-up of 25 months. The 1-year functional patency rates were 67%±2.0% for RCAVFs, 83%±2.0% for upper arm AVFs, and 85%±3.5% for AVGs. Three-year functional patency rates were 62%±2.0% for RCAVFs, 74%±2.0% for upper arm AVFs, and 69%±5% for AVGs. AVGs required more procedures per year (3.3 per year) of functional patency when compared with upper arm AVFs (1.8 per year). Conclusions: The functional patency of AVFs and AVGs is comparable, although AVGs required more interventions to maintain usability for HD. The choice of VA is a trade-off between short-term advantages, favoring AVGs, and long-term advantages, favoring AVFs. Which VA is most appropriate depends on the patient's prognosis and preferences.

Endovascular salvage of non-maturing autogenous arteriovenous fistulas by using angioplasty and competitive vein embolization.

INTRODUCTION: The aim of this study is to evaluate the maturation and patency rates after endovascular treatment of non-maturing arteriovenous fistulas with percutaneous transluminal angioplasty, embolization of competitive veins, or a combination of both in a series of consecutive patients. MATERIAL AND METHODS: Retrospective evaluation of patients with non-matured arteriovenous fistulas treated in our hospital was performed. Fistulography and ultrasonography was performed in all patients to evaluate the presence of stenosis and competitive veins. Significant stenoses (> 50%) were treated with balloon angioplasty and competitive veins (accessory and collateral veins) with coil embolization. RESULTS: A total of 78 fistulas were treated. Angioplasty and coil embolization were performed in 73 and 51 patients, respectively. No major complications occurred. In 65 out of 78 arteriovenous fistulas (83%), successful cannulation with two needles was possible after endovascular treatment. Sixty-three arteriovenous fistulas (81%) were used successfully for at least 3 months. Accessory veins were the only lesion present in 14% of the arteriovenous fistulas; coil embolization of these accessory veins resulted in 100% successful maturation. The estimated 3, 6, and 12 months postintervention assisted primary patency rates were, respectively, 73%, 55%, and 45%. The estimated 3, 6, and 12 months postintervention secondary patency rates were, respectively, 81%, 78%, and 73%. CONCLUSION AND DISCUSSION: Angioplasty and coil embolization are successful and safe procedures that can convert a non-mature fistula into a mature one in more than 80% of patients. Accessory vein embolization may be more important than collateral vein embolization in the presence of stenosis.

Comparison of different adult stem cell types for treatment of myocardial ischemia.

BACKGROUND: A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction. METHODS AND RESULTS: Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially received one cell type (5x10(5)) or PBS. Cell survival was measured by BLI and by TaqMan PCR. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements. Fluc expression correlated with cell number in all groups (r(2)>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes. CONCLUSIONS: This is the first study to show that compared to MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function.

A review of current approaches for evaluating impaired performance in around-the-clock medical professionals.

The need for data to study the relationship between fatigued healthcare professionals and performance outcomes is evident, however, it is unclear which methodology is most appropriate to provide these insights. To address this issue, we performed a systematic review of relevant articles by searching the MEDLINE, EMBASE, Cochrane, Web of Science, and CINAHL databases. The literature search identified 2960 unique references, of which 82 were identified eligible. The impact on performance was studied on clinical outcomes, medical simulation, neurocognitive performance, sleep quantification and subjective assessment. In general results on performance are conflicting; impairment, no effect, and improvement were found. This review outlines the various methods currently available for assessing fatigue-impaired performance. The contrasting outcomes can be attributed to three main factors: differences in the operationalisation of fatigue, incomplete control data, and the wide variety in the methods used. We recommend the implementation of a clinically applicable tool that can provide uniform data. Until these data become available, caution should be used when developing regulations that can have implications for physicians, education, manpower planning, and ‒ ultimately ‒ patient care.

Resection of carotid body tumors: results of an evolving surgical technique.

OBJECTIVE: To evaluate a modified technique for carotid body tumor (CBT) resection. BACKGROUND: Resection of CBT can lead to substantial postoperative morbidity because of a rich vascularization and close connection to neurovascular structures. The impact of a modified surgical technique on postoperative outcome was evaluated and compared with a historical group and the literature. METHODS: Medical records of patients who underwent CBT surgery at Leiden University Medical Center between 1963 and 2005 were retrospectively reviewed. Before 1992, a standard approach was conducted. After 1992, most tumors were resected using an alternative technique, working in a craniocaudal fashion from skull base to carotid bifurcation. Data were reported as details of the pre, intra-, and postoperative periods. RESULTS: A total of 111 CBT resections (69 standard, 42 craniocaudal) were performed in 94 patients (44 male/50 female, mean age 41). The standard group consisted of 39 Shamblin I (56%), 22 II (32%), and 8 III (12%) tumors. The craniocaudally approached CBT included 12 Shamblin I (29%), 13 II (31%), and 17 III (40%) tumors. The mean blood loss was 901 mL (standard operations) versus 281 mL (craniocaudal approach, P < 0.0005). Persistent cranial nerve damage was encountered after 26 (23%) of 111 operations; 21 after the standard operations (30% within this group, including 3 preexistent nonresolved cranial nerve deficits); and 5 (12%, including 2 due to additional vagal body resections) after the craniocaudal operations (P = 0.025). CONCLUSIONS: The craniocaudal dissection technique of a CBT can be applied with little blood loss, thereby reducing the risk of postoperative morbidity.