An Extended Hierarchical Task Analysis for Error Prediction in Medical Devices

This paper introduces an extended hierarchical task analysis (HTA) methodology devised to evaluate and compare user interfaces on volumetric infusion pumps. The pumps were studied along the dimensions of overall usability and propensity for generating human error. With HTA as our framework, we analyzed six pumps on a variety of common tasks using Norman’s Action theory. The introduced method of evaluation divides the problem space between the external world of the device interface and the user’s internal cognitive world, allowing for predictions of potential user errors at the human-device level. In this paper, one detailed analysis is provided as an example, comparing two different pumps on two separate tasks. The results demonstrate the inherent variation, often the cause of usage errors, found with infusion pumps being used in hospitals today. The reported methodology is a useful tool for evaluating human performance and predicting potential user errors with infusion pumps and other simple medical devices.

ANALYSIS OF THE CORYNEBACTERIUM PARVUM-INDUCED DECLINE OF MURINE NATURAL KILLER CELL-MEDIATED CYTOTOXICITY

Treatment of mice with the immunomodulating agent, Corynebacterium parvum (C. parvum), was shown to result in a severe and long-lasting depression of splenic natural killer (NK) cell-mediated cytotoxicity 5-21 days post-inoculation. Because NK cells have been implicated in immunosurveillance against malignancy (due to their spontaneous occurrence and rapid reactivity to a variety of histological types of tumors), as well as in resistance to established tumors, this decreased activity was of particular concern, since this effect is contrary to that which would be considered therapeutically desirable in cancer treatment (i.e. a potentiation of antitumor effector functions, including NK cell activity, would be expected to lead to a more effective destruction of malignant cells). Therefore, an analysis of the mechanism of this decline of splenic NK cell activity in C.parvum treated mice was undertaken.^ From in vitro co-culturing experiments, it was found that low NK-responsive C. parvum splenocytes were capable of reducing the normally high-reactivity of cells from untreated syngeneic mice to YAC-1 lymphoma, suggesting the presence of NK-directed suppressor cells in C. parvum treated animals. This was further supported by the demonstration of normal levels of cytotoxicity in C. parvum splenocyte preparations following Ficoll-Hypaque separation, which coincided with removal of the NK-suppressive capabilities of these cells. The T cell nature of these regulatory cells was indicated by (1) the failure of C. parvum to cause a reduction of NK cell activity, or the generation of NK-directed suppressor cells in T cell-deficient athymic mice, (2) the removal of C. parvum-induced suppression by T cell-depleting fractionation procedures or treatments, and (3) demonstration of suppression of NK cell activity by T cell-enriched C. parvum splenocytes. These studies suggest, therefore, that the eventual reduction of suppression by T cell elimination and/or inhibition, may result in a promotion of the antitumor effectiveness of C. parvum due to the contribution of "freed" NK effector cell activity.^ However, the temporary suppression of NK cell activity induced by C. parvum (reactivity of treated mice returns to normal levels within 28 days after C. parvum injection), may in fact be favorable in some situations, e.g. in bone marrow transplantation cases, since NK cells have been suggested to play a role also in the process of bone marrow graft rejection.^ Therefore, the discriminate use of agents such as C. parvum may allow for the controlled regulation of NK cell activity suggested to be necessary for the optimalization of therapeutic regimens. ^

Cross-cultural analysis of type D (distressed) personality in 6222 patients with ischemic heart disease: a study from the International HeartQoL Project

BACKGROUND Type D (distressed) personality, the conjoint effect of negative affectivity (NA) and social inhibition (SI), predicts adverse cardiovascular outcomes, and is assessed with the 14-item Type D Scale (DS14). However, potential cross-cultural differences in Type D have not been examined yet in a direct comparison of countries. AIM To examine the cross-cultural validity of the Type D construct and its relation with cardiovascular risk factors, cardiac symptom severity, and depression/anxiety. METHODS In 22 countries, 6222 patients with ischemic heart disease (angina, 33%; myocardial infarction, 37%; or heart failure, 30%) completed the DS14 as part of the International HeartQoL Project. RESULTS Type D personality was assessed reliably across countries (αNA>.80; αSI>.74; except Russia, which was excluded from further analysis). Cross-cultural measurement equivalence was established for Type D personality at all measurement levels, as the factor-item configuration, factor loadings, and error structure were not different across countries (fit: CFI=.91; NFI=.88; RMSEA=.018), as well as across gender and diagnostic subgroups. Type D personality was more prevalent in Southern (37%) and Eastern (35%) European countries compared to Northern (24%) and Western European and English-speaking (both 27%) countries (p<.001). Type D was not confounded by cardiac symptom severity, but was associated with a higher prevalence of hypertension, smoking, sedentary lifestyle, and depression. CONCLUSION Cross-cultural measurement equivalence was demonstrated for the Type D scale in 21 countries. There is a pan-cultural relationship between Type D personality and some cardiovascular risk factors, supporting the role of Type D personality across countries and cardiac conditions.

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

A quantitative analysis of microcirculation in sore-prone pressure areas on conventional and pressure relief hospital mattresses using laser Doppler flowmetry and tissue spectrophotometry

BACKGROUND Pressure ulcers are associated with severe impairment for the patients and high economic load. With this study we wanted to gain more insight to the skin perfusion dynamics due to external loading. Furthermore, we evaluated the effect of different types of pressure relief mattresses. METHODS A total of 25 healthy volunteers were enrolled in the study. Perfusion dynamics of the sacral and the heel area were assessed using the O2C-device, which combines a laser light, to determine blood flow, and white light to determine the relative amount of hemoglobin. Three mattresses were evaluated compared to a hard surface: a standard hospital foam mattress bed, a visco-elastic foam mattress, and an air-fluidized bed. RESULTS In the heel area, only the air-fluidized bed was able to maintain the blood circulation (mean blood flow of 13.6 ± 6 versus 3.9 ± 3 AU and mean relative amount of hemoglobin of 44.0 ± 14 versus 32.7 ± 12 AU.) In the sacral area, all used mattresses revealed an improvement of blood circulation compared to the hard surface. CONCLUSION The results of this study form a more precise pattern of perfusion changes due to external loading on various pressure relief mattresses. This knowledge may reduce the incidence of pressure ulcers and may be an influencing factor in pressure relief mattress selection.

New online method for water isotope analysis of speleothem fluid inclusions using laser absorption spectroscopy (WS-CRDS)

A new online method to analyse water isotopes of speleothem fluid inclusions using a wavelength scanned cavity ring down spectroscopy (WS-CRDS) instrument is presented. This novel technique allows us simultaneously to measure hydrogen and oxygen isotopes for a released aliquot of water. To do so, we designed a new simple line that allows the online water extraction and isotope analysis of speleothem samples. The specificity of the method lies in the fact that fluid inclusions release is made on a standard water background, which mainly improves the δ D robustness. To saturate the line, a peristaltic pump continuously injects standard water into the line that is permanently heated to 140 °C and flushed with dry nitrogen gas. This permits instantaneous and complete vaporisation of the standard water, resulting in an artificial water background with well-known δ D and δ18O values. The speleothem sample is placed in a copper tube, attached to the line, and after system stabilisation it is crushed using a simple hydraulic device to liberate speleothem fluid inclusions water. The released water is carried by the nitrogen/standard water gas stream directly to a Picarro L1102-i for isotope determination. To test the accuracy and reproducibility of the line and to measure standard water during speleothem measurements, a syringe injection unit was added to the line. Peak evaluation is done similarly as in gas chromatography to obtain &delta D; and δ18O isotopic compositions of measured water aliquots. Precision is better than 1.5 ‰ for δ D and 0.4 ‰ for δ18O for water measurements for an extended range (−210 to 0 ‰ for δ D and −27 to 0 ‰ for δ18O) primarily dependent on the amount of water released from speleothem fluid inclusions and secondarily on the isotopic composition of the sample. The results show that WS-CRDS technology is suitable for speleothem fluid inclusion measurements and gives results that are comparable to the isotope ratio mass spectrometry (IRMS) technique.

Effects of Thoratec pulsatile ventricular assist device (PVAD) timing on the abdominal aortic wave intensity pattern

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculo-aortic cannulation. The start of PVAD ejection was synchronized to the native R-wave and delayed between 0 % - 90 % of the cardiac cycle in 10 % steps or phase shifts (PS). Pressure and velocity signals were registered, using a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe, that non-invasive WIA could potentially be used clinically to assess the mechanical load of the LV, and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis

BACKGROUND Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. METHODS AND RESULTS Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. CONCLUSIONS The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals.

The use of bougie-guided insertion of a laryngeal mask airway device in neonatal piglets after unexpected complications

After marked airway obstruction with laryngeal mask (LM) placement in neonate piglets, anatomical observations in cadavers revealed a large epiglottis advancing markedly over the soft palate. CT imaging in vivo confirmed that the LM pushes the epiglottis caudally thereby obstructing the larynx. As a new approach, in 20 piglets a flexible PVC bougie placed under laryngoscopy was used to guide the LM to the correct position at the larynx. Placement of the bougie was easy and the LM was positioned successfully in all piglets at first attempt. In 14 piglets, the epiglottis was positioned dorsal to the soft palate before LM insertion and had to be pushed downwards to advance the bougie. In case of failure of LM placement with potential airway obstruction, the use of a bougie to guide the LM over the epiglottis was simple, rapid, and improved the success rate without complication.

Complication and failure rates with implant-supported fixed dental prostheses and single crowns: a 10-year retrospective study

PURPOSE Clinical studies related to the long-term outcomes with implant-supported reconstructions are still sparse. The aim of this 10-year retrospective study was to assess the rate of mechanical/technical complications and failures with implant supported fixed dental prostheses (FDPs) and single crowns (SCs) in a large cohort of partially edentulous patients. MATERIALS AND METHODS The comprehensive multidisciplinary examination consisted of a medical/dental history, clinical examination, and a radiographic analysis. Prosthodontic examination evaluated the implant-supported reconstructions for mechanical/technical complications and failures, occlusal analysis, presence/absence of attrition, and location, extension, and retention type. RESULTS Out of three hundred ninety seven fixed reconstructions in three hundred three patients, two hundred sixty eight were SCs and one hundred twenty seven were FDPs. Of these three hundred ninety seven implant-supported reconstructions, 18 had failed, yielding a failure rate of 4.5% and a survival rate of 95.5% after a mean observation period of 10.75 years (range: 8.4-13.5 years). The most frequent complication was ceramic chipping (20.31%) followed by occlusal screw loosening (2.57%) and loss of retention (2.06%). No occlusal screw fracture, one abutment loosening, and two abutment fractures were noted. This resulted in a total mechanical/technical complication rate of 24.7%. The prosthetic success rate over a mean follow-up time of 10.75 years was 70.8%. Generalized attrition and FDPs were associated with statistically significantly higher rates of ceramic fractures when compared with SCs. Cantilever extensions, screw retention, anterior versus posterior, and gender did not influence the chipping rate. CONCLUSIONS After a mean exposure time of 10.75 years, high survival rates for reconstructions supported by Sand-blasted Large-grit Acid-etched implants can be expected. Ceramic chipping was the most frequent complication and was increased in dentitions with attrition and in FDPs compared with SCs.

Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

Favourable mid-term outcome after heart transplantation for late Fontan failure.

OBJECTIVES Fontan failure (FF) represents a growing and challenging indication for paediatric orthotopic heart transplantation (OHT). The aim of this study was to identify predictors of the best mid-term outcome in OHT after FF. METHODS Twenty-year multi-institutional retrospective analysis on OHT for FF. RESULTS Between 1991 and 2011, 61 patients, mean age 15.0 ± 9.7 years, underwent OHT for failing atriopulmonary connection (17 patients = 27.8%) or total cavopulmonary connection (44 patients = 72.2%). Modality of FF included arrhythmia (14.8%), complex obstructions in the Fontan circuit (16.4%), protein-losing enteropathy (PLE) (22.9%), impaired ventricular function (31.1%) or a combination of the above (14.8%). The mean time interval between Fontan completion and OHT was 10.7 ± 6.6 years. Early FF occurred in 18%, requiring OHT 0.8 ± 0.5 years after Fontan. The hospital mortality rate was 18.3%, mainly secondary to infection (36.4%) and graft failure (27.3%). The mean follow-up was 66.8 ± 54.2 months. The overall Kaplan-Meier survival estimate was 81.9 ± 1.8% at 1 year, 73 ± 2.7% at 5 years and 56.8 ± 4.3% at 10 years. The Kaplan-Meier 5-year survival estimate was 82.3 ± 5.9% in late FF and 32.7 ± 15.0% in early FF (P = 0.0007). Late FF with poor ventricular function exhibited a 91.5 ± 5.8% 5-year OHT survival. PLE was cured in 77.7% of hospital survivors, but the 5-year Kaplan-Meier survival estimate in PLE was 46.3 ± 14.4 vs 84.3 ± 5.5% in non-PLE (P = 0.0147). Cox proportional hazards identified early FF (P = 0.0005), complex Fontan pathway obstruction (P = 0.0043) and PLE (P = 0.0033) as independent predictors of 5-year mortality. CONCLUSIONS OHT is an excellent surgical option for late FF with impaired ventricular function. Protein dispersion improves with OHT, but PLE negatively affects the mid-term OHT outcome, mainly for early infective complications.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK - a nested case-control analysis

AIMS To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.