Assessing the impact of DRGs on patient care and professional practice in Switzerland (IDoC) : a potential model for monitoring and evaluating healthcare reform.

QUESTIONS UNDER STUDY: The starting point of the interdisciplinary project "Assessing the impact of diagnosis related groups (DRGs) on patient care and professional practice" (IDoC) was the lack of a systematic ethical assessment for the introduction of cost containment measures in healthcare. Our aim was to contribute to the methodological and empirical basis of such an assessment. METHODS: Five sub-groups conducted separate but related research within the fields of biomedical ethics, law, nursing sciences and health services, applying a number of complementary methodological approaches. The individual research projects were framed within an overall ethical matrix. Workshops and bilateral meetings were held to identify and elaborate joint research themes. RESULTS: Four common, ethically relevant themes emerged in the results of the studies across sub-groups: (1.) the quality and safety of patient care, (2.) the state of professional practice of physicians and nurses, (3.) changes in incentives structure, (4.) vulnerable groups and access to healthcare services. Furthermore, much-needed data for future comparative research has been collected and some early insights into the potential impact of DRGs are outlined. CONCLUSIONS: Based on the joint results we developed preliminary recommendations related to conceptual analysis, methodological refinement, monitoring and implementation.

Using step activity monitoring to assess ambulatory activity before and after total ankle arthroplasty : FM103

Introduction: The aim of this study is to compare the walking activity of a cohort of individuals before and after total ankle arthroplasty (TAA). Methods: Nineteen consecutive patients (ten males and nine females) with mean age of 58.72, selected for TAA between January and June 2006, were prospectively reviewed with the use of a dedicated ambulatory activity-monitoring device to assess their natural ambulatory activity. Patients were tested in the community for two weeks duration, one month prior to and at least eighteen months after surgery. The ambulatory parameters were assessed through measurement of the number of steps at different cadence, and the time spent walking at different walking paces. Data were analyzed by using specific statistical methods. Results: This study revealed a significant improvement in the number of steps walked at normal cadence (b = 331.63, p = .00) and significantly reduced at low cadence (b = -402.52, p = .00) and medium cadence (b = -386.29, p = .00), before and after TAA. However, there are no significant different between two phases of assessment in term of time spent walking. Conclusion: These quantitative data allow a clear comparative assessment of walking ability following TAR and demonstrates that this intervention improves patient's walking pace.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Prospective monitoring of cefepime in intensive care unit adult patients.

INTRODUCTION: Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia. METHODS: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis. RESULTS: Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC <or= 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC >or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest. CONCLUSIONS: These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs <or= 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.

Assessing the Functionality and Biocompatibility of a Wireless Contact Lens Sensor for 24 hour-intraocular Pressure Monitoring in Volunteers: Preliminary Results

Purpose: In vitro studies in porcine eyes have demonstrated a good correlation between induced intraocular pressure variations and corneal curvature changes, using a contact lens with an embedded microfabricated strain gauge. Continuous 24 hour-intraocular pressure (IOP) monitoring to detect large diurnal fluctuation is currently an unmet clinical need. The aims of this study is to evaluate precision of signal transmission and biocompatibility of 24 hour contact lens sensor wear (SENSIMED Triggerfish®) in humans. Methods: After full eye examination in 10 healthy volunteers, a 8.7 mm radius contact lens sensor and an orbital bandage containing a loop antenna were applied and connected to a portable recorder. Best corrected visual acuity and position, lubrication status and mobility of the sensor were assessed after 5 and 30 minutes, 4, 7 and 24 hours. Subjective comfort was scored and activities documented in a logbook. After sensor removal full eye examination was repeated, and the registration signal studied. Results: The comfort score was high and did not fluctuate significantly, except at the 7 hour-visit. The mobility of the contact lens was minimal but its lubrication remained good. Best corrected visual acuity was significantly reduced during the sensor wear and immediately after its removal. Three patients developed mild corneal staining. In all but one participant we obtained a registration IOP curve with visible ocular pulse amplitude. Conclusions: This 24 hour-trial confirmed the functionality and biocompatibility of SENSIMED Triggerfish® wireless contact lens sensor for IOP-fluctuation monitoring in volunteers. Further studies with a range of different contact lens sensor radii are indicated.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Monitoring of malaria parasite resistance to chloroquine and sulphadoxine-pyrimethamine in the Solomon Islands by DNA microarray technology.

BACKGROUND: Little information is available on resistance to anti-malarial drugs in the Solomon Islands (SI). The analysis of single nucleotide polymorphisms (SNPs) in drug resistance associated parasite genes is a potential alternative to classical time- and resource-consuming in vivo studies to monitor drug resistance. Mutations in pfmdr1 and pfcrt were shown to indicate chloroquine (CQ) resistance, mutations in pfdhfr and pfdhps indicate sulphadoxine-pyrimethamine (SP) resistance, and mutations in pfATPase6 indicate resistance to artemisinin derivatives. METHODS: The relationship between the rate of treatment failure among 25 symptomatic Plasmodium falciparum-infected patients presenting at the clinic and the pattern of resistance-associated SNPs in P. falciparum infecting 76 asymptomatic individuals from the surrounding population was investigated. The study was conducted in the SI in 2004. Patients presenting at a local clinic with microscopically confirmed P. falciparum malaria were recruited and treated with CQ+SP. Rates of treatment failure were estimated during a 28-day follow-up period. In parallel, a DNA microarray technology was used to analyse mutations associated with CQ, SP, and artemisinin derivative resistance among samples from the asymptomatic community. Mutation and haplotype frequencies were determined, as well as the multiplicity of infection. RESULTS: The in vivo study showed an efficacy of 88% for CQ+SP to treat P. falciparum infections. DNA microarray analyses indicated a low diversity in the parasite population with one major haplotype present in 98.7% of the cases. It was composed of fixed mutations at position 86 in pfmdr1, positions 72, 75, 76, 220, 326 and 356 in pfcrt, and positions 59 and 108 in pfdhfr. No mutation was observed in pfdhps or in pfATPase6. The mean multiplicity of infection was 1.39. CONCLUSION: This work provides the first insight into drug resistance markers of P. falciparum in the SI. The obtained results indicated the presence of a very homogenous P. falciparum population circulating in the community. Although CQ+SP could still clear most infections, seven fixed mutations associated with CQ resistance and two fixed mutations related to SP resistance were observed. Whether the absence of mutations in pfATPase6 indicates the efficacy of artemisinin derivatives remains to be proven.

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

Age differences in biological monitoring of chemical exposure: a tentative description using a toxicokinetic model

AIM: Specific factors responsible for interindividual variability should be identified and their contribution quantified to improve the usefulness of biological monitoring. Among others, age is an easily identifiable determinant, which could play an important impact on biological variability. MATERIALS AND METHODS: A compartmental toxicokinetic model developed in previous studies for a series of metallic and organic compounds was applied to the description of age differences. Young male physiological and metabolic parameters, based on Reference Man information, were taken from preceding studies and were modified to take into account age based on available information about age differences. RESULTS: Numerical simulation using the kinetic model with the modified parameters indicates in some cases important differences due to age. The expected changes are mostly of the order of 10-20%, but differences up to 50% were observed in some cases. CONCLUSION: These differences appear to depend on the chemical and on the biological entity considered. Further work should be done to improve our estimates of these parameters, by considering for example uncertainty and variability in these parameters. [Authors]

Monitoring the clinical introduction of a glutamine and antioxidant solution in critically ill trauma and burn patients

OBJECTIVE: Enteral glutamine supplementation and antioxidants have been shown to be beneficial in some categories of critically ill patients. This study investigated the impact on organ function and clinical outcome of an enteral solution enriched with glutamine and antioxidant micronutrients in patients with trauma and with burns. METHODS: This was a prospective study of a historical control group including critically ill, burned and major trauma patients (n = 86, 40 patients with burns and 46 with trauma, 43 in each group) on admission to an intensive care unit in a university hospital (matching for severity, age, and sex). The intervention aimed to deliver a 500-mL enteral solution containing 30 g of glutamine per day, selenium, zinc, and vitamin E (Gln-AOX) for a maximum of 10 d, in addition to control treatment consisting of enteral nutrition in all patients and intravenous trace elements in all burn patients. RESULTS: Patients were comparable at baseline, except for more inhalation injuries in the burn-Gln-AOX group (P = 0.10) and greater neurologic impairment in the trauma-Gln-AOX group (P = 0.022). Intestinal tolerance was good. The full 500-mL dose was rarely delivered, resulting in a low mean glutamine daily dose (22 g for burn patients and 16 g for trauma patients). In burn patients intravenous trace element delivery was superior to the enteral dose. The evolution of the Sequential Organ Failure Assessment score and other outcome variables did not differ significantly between groups. C-reactive protein decreased faster in the Gln-AOX group. CONCLUSION: The Gln-AOX supplement was well tolerated in critically ill, injured patients, but did not improve outcome significantly. The delivery of glutamine below the 0.5-g/kg recommended dose in association with high intravenous trace element substitution doses in burn patients are likely to have blunted the impact by not reaching an efficient treatment dose. Further trials testing higher doses of Gln are required.

Impact of electronic monitoring of drug adherence on blood pressure control in primary care: a cluster 12-month randomised controlled study.

BACKGROUND: Poor long-term adherence is an important cause of uncontrolled hypertension. We examined whether monitoring drug adherence with an electronic system improves long-term blood pressure (BP) control in hypertensive patients followed by general practitioners (GPs). METHODS: A pragmatic cluster randomised controlled study was conducted over one year in community pharmacists/GPs' networks randomly assigned either to usual care (UC) where drugs were dispensed as usual, or to intervention (INT) group where drug adherence could be monitored with an electronic system (Medication Event Monitoring System). No therapy change was allowed during the first 2 months in both groups. Thereafter, GPs could modify therapy and use electronic monitors freely in the INT group. The primary outcome was a target office BP<140/90 mmHg. RESULTS: Sixty-eight treated uncontrolled hypertensive patients (UC: 34; INT: 34) were enrolled. Over the 12-month period, the likelihood of reaching the target BP was higher in the INT group compared to the UC group (p<0.05). At 4 months, 38% in the INT group reached the target BP vs. 12% in the UC group (p<0.05), and 21% vs. 9% at 12 months (p: ns). Multivariate analyses, taking account of baseline characteristics, therapy modification during follow-up, and clustering effects by network, indicate that being allocated to the INT group was associated with a greater odds of reaching the target BP at 4 months (p<0.01) and at 12 months (p=0.051). CONCLUSION: GPs monitoring drug adherence in collaboration with pharmacists achieved a better BP control in hypertensive patients, although the impact of monitoring decreased with time.

Reproducibility of species lists, visual cover estimates and frequency methods for recording high mountain vegetation

Question: When multiple observers record the same spatial units of alpine vegetation, how much variation is there in the records and what are the consequences of this variation for monitoring schemes to detect change? Location: One test summit in Switzerland (Alps) and one test summit in Scotland (Cairngorm Mountains). Method: Eight observers used the GLORIA protocols for species composition and visual cover estimates in percent on large summit sections (>100 m2) and species composition and frequency in nested quadrats (1 m2). Results: The multiple records from the same spatial unit for species composition and species cover showed considerable variation in the two countries. Estimates of pseudoturnover of composition and coefficients of variation of cover estimates for vascular plant species in 1m x 1m quadrats showed less variation than in previously published reports whereas our results in larger sections were broadly in line with previous reports. In Scotland, estimates for bryophytes and lichens were more variable than for vascular plants. Conclusions: Statistical power calculations indicated that, unless large numbers of plots were used, changes in cover or frequency were only likely to be detected for abundant species (exceeding 10% cover) or if relative changes were large (50% or more). Lower variation could be reached with the point methods and with larger numbers of small plots. However, as summits often strongly differ from each other, supplementary summits cannot be considered as a way of increasing statistical power without introducing a supplementary component of variance into the analysis and hence the power calculations.

Retrofit Methods for Distortion Cracking Problems in Plate Girder Bridges, TR-436, 2003

This report is formatted to independently present four individual investigations related to similar web gap fatigue problems. Multiple steel girder bridges commonly exhibit fatigue cracking due to out-of-plane displacement of the web near the diaphragm connections. This fatigue-prone web gap area is typically located in negative moment regions of the girders where the diaphragm stiffener is not attached to the top flange. In the past, the Iowa Department of Transportation has attempted to stop fatigue crack propagation in these steel girder bridges by drilling holes at the crack tips. Other nondestructive retrofits have been tried; in a particular case on a two-girder bridge with floor beams, angles were bolted between the stiffener and top flange. The bolted angle retrofit has failed in the past and may not be a viable solution for diaphragm bridges. The drilled hole retrofit is often only a temporary solution, so a more permanent and effective retrofit is required. A new field retrofit has been developed that involves loosening the bolts in the connection between the diaphragm and the girders. Research on the retrofit has been initiated; however, no long-term studies of the effects of bolt loosening have been performed. The intent of this research is to study the short-term effects of the bolt loosening retrofit on I-beam and channel diaphragm bridges. The research also addressed the development of a continuous remote monitoring system to investigate the bolt loosening retrofit on an X-type diaphragm bridge over a number of months, ensuring that the measured strain and displacement reductions are not affected by time and continuous traffic loading on the bridge. The testing for the first three investigations is based on instrumentation of web gaps in a negative moment region on Iowa Department of Transportation bridges with I-beam, channel, and X-type diaphragms. One bridge of each type was instrumented with strain gages and deflection transducers. Field tests, using loaded trucks of known weight and configuration, were conducted on the bridges with the bolts in the tight condition and after implementing the bolt loosening retrofit to measure the effects of loosening the diaphragm bolts. Long-term data were also collected on the X-diaphragm bridge by a data acquisition system that collected the data continuously under ambient truck loading. The collected data were retrievable by an off-site modem connection to the remote data acquisition system. The data collection features and ruggedness of this system for remote bridge monitoring make it viable as a pilot system for future monitoring projects in Iowa. Results indicate that loosening the diaphragm bolts reduces strain and out-of-plane displacement in the web gap, and that the reduction is not affected over time by traffic or environmental loading on the bridge. Reducing the strain in the web gap allows the bridge to support more cycles of loading before experiencing fatigue, thus increase the service life of the bridge. Two-girder floor beam bridges may also exhibit fatigue cracking in girder webs.

A Feasibility Study on Embedded Micro-Electromechanical Sensors and Systems (MEMS) for Monitoring Highway Structures, TR-575, 2011

Micro-electromechanical systems (MEMS) provide vast improvements over existing sensing methods in the context of structural health monitoring (SHM) of highway infrastructure systems, including improved system reliability, improved longevity and enhanced system performance, improved safety against natural hazards and vibrations, and a reduction in life cycle cost in both operating and maintaining the infrastructure. Advancements in MEMS technology and wireless sensor networks provide opportunities for long-term continuous, real-time structural health monitoring of pavements and bridges at low cost within the context of sustainable infrastructure systems. The primary objective of this research was to investigate the use of MEMS in highway structures for health monitoring purposes. This study focused on investigating the use of MEMS and their potential applications in concrete through a comprehensive literature review, a vendor survey, and a laboratory study, as well as a small-scale field study. Based on the comprehensive literature review and vendor survey, the latest information available on off-the-shelf MEMS devices, as well as research prototypes, for bridge, pavement, and traffic applications were synthesized. A commercially-available wireless concrete monitoring system based on radio-frequency identification (RFID) technology and off-the-shelf temperature and humidity sensors were tested under controlled laboratory and field conditions. The test results validated the ability of the RFID wireless concrete monitoring system in accurately measuring the temperature both inside the laboratory and in the field under severe weather conditions. In consultation with the project technical advisory committee (TAC), the most relevant MEMS-based transportation infrastructure research applications to explore in the future were also highlighted and summarized.