Reference values for maximum work rate in apparently healthy Dutch/Flemish adults: data from the LowLands fitness registry.

Background: The peak oxygen uptake (VO2peak) test is the gold standard for cardiorespiratory fitness. However, the test is demanding, requiring sophisticated apparatus for measuring the oxygen uptake. Peak work rate (WRpeak) testing is a promising substitute for peak VO2peak testing. However, there is a paucity of research conducted to determine reference values (RVs) for WRpeak. Methods: The database from the LowLands fitness registry was used, containing data from health checks from apparently healthy subjects among various professions. Exercise tests were performed using a cycle ergometer and a calibrated metabolic cart. Analysis was executed on 3463 subjects, 2868 male and 595 female. Reference values with corresponding centiles were developed using the LMS method. Results: VO2peak and WRpeak where highly associated with Pearson's correlation of 0.9 (p = .001). Weight, height, maximum heart rate, and the respiratory exchange ratio had a positive significant effect (p < .001) on WRpeak, and age a negative significant effect, in both males and females. The following formulas were computed for RVs: WRpeak=-102+(1.5 * weight[kg])+(1.9 * height[cm])-(2.0 * age)-(sex * 60[M:0;V:1]) WRpeak/kg=2.45-(0.026 * weight[kg])+(0.024 * height[cm])-(0.024 * age)-(sex * 0.84 [M:0;V:1]) Conclusions: WRpeak can be used as a substitute for VO2peak when a respiratory gas-analysis system is not available. This study provides RVs for WRpeak and WRpeak/kg in a healthy Dutch/Flemish adult population using cycle ergometry. Further research is needed to obtain RVs for elderly subjects, specific diseases, ethnicities and ergometers.

Effects of a pre-operative home-based inspiratory muscle training programme on perceived health-related quality of life in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: Pre-operative inspiratory muscle training has been shown to decrease the incidence of postoperative pneumonia and length of hospital stay in patients undergoing coronary artery bypass graft surgery (CABG). This study investigated if this decrease acted as a mediator on the time course of quality of life. DESIGN: Complementary analyses of a published randomised controlled trial. SETTING AND PARTICIPANTS: The initial trial included patients awaiting CABG surgery at a Dutch university hospital. The secondary analyses used data from the initial trial for patients who had completed at least one quality-of-life questionnaire. METHODS: Participants were allocated at random to the intervention group or the usual care group. The intervention group followed a home-based pre-operative inspiratory muscle training programme. Quality of life was measured at five time points. Between-group differences in quality-of-life scores were analysed using mixed linear modelling. RESULTS: The secondary analyses used data for 235 patients. In line with the initial trial, pneumonia and length of hospital stay were decreased significantly in the intervention group. The time courses for all patients showed significant improvements in quality of life after surgery compared with baseline. No significant differences in quality of life were observed over time between the two groups. CONCLUSION: Despite decreased incidence of pneumonia and length of hospital stay in the intervention group, this study did not find any improvements in quality of life due to the pre-operative home-based inspiratory muscle training programme. Clinical trial registration number ISRCTN17691887.

Relationship between lung function and Modified Shuttle Test performance in adult patients with cystic fibrosis: a cross-sectional, retrospective study.

OBJECTIVES: To investigate the relationship between lung function and exercise capacity in adults with cystic fibrosis (CF), and to develop a CF-specific equation to predict Modified Shuttle Test (MST) performance from baseline data. DESIGN: Cross-sectional, retrospective study. SETTING: Adult CF centre. PARTICIPANTS: One hundred and twenty-seven patients with CF [61 male; mean age 25 years (range 17 to 52 years), mean forced expiratory volume in 1second (FEV1) 56% predicted (range 15 to 124%)]. MAIN OUTCOME MEASURES: MST and FEV1. RESULTS: Overall, a moderate-to-good relationship was found between lung function and MST performance (walking distance vs FEV1% predicted: r=0.64, P=0.01). This relationship between FEV1 and MST shows an obvious threshold at an FEV1 of 67% predicted. Above this threshold, no significant association was observed between FEV1 and MST performance. However, a strong relationship (MST vs FEV1% predicted: r≥0.74, P<0.01 for men and r=0.79, P<0.01 for women) was found below an FEV1 of 67% predicted. CONCLUSIONS: This study suggests that a strong association exists between lung function (FEV1% predicted) and MST (walking distance) in adult patients with moderate-to-severe CF (FEV1<67% predicted). A reference equation for MST performance was developed for those patients with FEV1 ≤67% predicted, providing a tool to make an a-priori prediction of MST walking distance.

Reference chart of inspiratory muscle strength: a new tool to monitor the effect of pre-operative training.

OBJECTIVES: To develop a reference chart to monitor inspiratory muscle strength during pre-operative inspiratory muscle training for patients at high risk of developing postoperative pulmonary complications awaiting coronary artery bypass graft (CABG) surgery. DESIGN: Secondary data analysis using patients from the intervention arm of a randomised clinical trial. SETTING: University medical centre. PARTICIPANTS: Patients at high risk of developing postoperative pulmonary complications awaiting CABG surgery. INTERVENTIONS: Patients performed inspiratory muscle training seven times per week for at least 2 weeks before surgery. MAIN OUTCOME MEASURES: Maximal inspiratory muscle strength. RESULTS: A new reference chart was produced using a non-linear time trend model with a normal error structure. CONCLUSIONS: The chart is a novel tool for monitoring the progress of inspiratory muscle training for physiotherapy practice. Wider use of this chart is recommended.

Cardiopulmonary exercise testing in congenital heart disease: equipment and test protocols.

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests as performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are very rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review exercise equipment and test protocols for CPET in children with congenital heart disease. (Neth Heart J 2009;17:339-44.).

Cardiopulmonary exercise testing in congenital heart disease: (contra)indications and interpretation.

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review the main indications for CPET in children with congenital heart disease, the contraindications for exercise testing and the indications for terminating an exercise test. Moreover, we will address the interpretation of gas exchange data from CPET in children with congenital heart disease. (Neth Heart J 2009;17:385-92.).

An evaluation of selected valid and mechanistically based SARs for skin sensitisation.

Skin sensitisation which clinically is manifested as allergic contact dermatitis is an important health endpoint to be taken into account in the risk assessment of chemicals. In the new EU chemical policy REACH, information on skin sensitisation potential will have to be provided for chemicals manufactured or imported equal to or above 1 tonne/year and it is estimated that the highest number of substances will need to be tested for skin sensitisation. Within REACH, the use of (Q)SARs and other alternative methods is strongly encouraged in order to reduce the number of animal tests. The goal of this project was to test the applicability of SARs and structural alerts for skin sensitisation in the REACH framework. SARs and structural alerts which were found in the literature were analysed and further refined by using a number of examples (substances) that had not been previously used in the derivation of the published SARs. For substances which fit within the boundaries of the proposed alerts, it is assumed that they would be classified as sensitising in accordance with EU classification and labelling rules.

[Fewer lung complications following inspiratory muscle training in patients undergoing coronary bypass surgery: a randomized trial]. / Minder longcomplicaties door ademspiertraining bij patiënten die een coronaire bypassoperatie moeten ondergaan: een gerandomiseerde trial.

OBJECTIVE: The aim of this study was to evaluate the prophylactic efficacy of preoperative physiotherapy, including inspiratory muscle training (IMT), on the incidence of postoperative pulmonary complications (PPCs) in high-risk patients scheduled for elective coronary artery bypass grafting (CABG). DESIGN: Randomized controlled clinical trial (www.controlled-trials. com/isrctn17691887). METHOD: Of 655 patients referred to a university medical centre in The Netherlands for elective CABG, 299 met the criteria for being at high risk of developing PPCs. A total of 279 were enrolled and monitored up to discharge from hospital. Patients were randomly assigned to receive either preoperative IMT (n=140) or usual care (n=139). Both groups received the same postoperative treatment. RESULTS: Both groups were comparable at baseline. Before CABG, 2 control group patients and 1 IMT group patient died. After CABG surgery, PPCs were present in 25 (18%) of 139 patients in the IMT group and 48 (35%) of 137 patients in the control group (OR: 0.52; 95% CI: 0.30-0.92). Pneumonia occurred in 9 (6.5%) of 139 patients in the IMT group and in 22 (16.1%) of 137 patients in the usual care group (OR: 0.40; 95% CI: 0.19-0.84). Mean duration of postoperative hospitalization was 7 (range 5-41) days in the IMT group versus 8 (range 6-70) days in the usual care group (Mann-Whitney test; Z: -2.42; p = 0.015). CONCLUSION: Preoperative physiotherapy, including IMT, statistically significantly reduced the incidence ofPPCs and the duration ofpostoperative hospitalization in patients at high risk of developing a pulmonary complication on undergoing CABG.

Global (Q)SARs for skin sensitisation: assessment against OECD principles.

As part of a European Chemicals Bureau contract relating to the evaluation of (Q)SARs for toxicological endpoints of regulatory importance, we have reviewed and analysed (Q)SARs for skin sensitisation. Here we consider some recently published global (Q)SAR approaches against the OECD principles and present re-analysis of the data. Our analyses indicate that "statistical" (Q)SARs which aim to be global in their applicability tend to be insufficiently robust mechanistically, leading to an unacceptably high failure rate. Our conclusions are that, for skin sensitisation, the mechanistic chemistry is very important and consequently the best non-animal approach currently applicable to predict skin sensitisation potential is with the help of an expert system. This would assign compounds into mechanistic applicability domains and apply mechanism-based (Q)SARs specific for those domains and, very importantly, recognise when a compound is outside its range of competence. In such situations, it would call for human expert input supported by experimental chemistry studies as necessary.

Validity and validation of expert (Q)SAR systems.

At a recent workshop in Setubal (Portugal) principles were drafted to assess the suitability of (quantitative) structure-activity relationships ((Q)SARs) for assessing the hazards and risks of chemicals. In the present study we applied some of the Setubal principles to test the validity of three (Q)SAR expert systems and validate the results. These principles include a mechanistic basis, the availability of a training set and validation. ECOSAR, BIOWIN and DEREK for Windows have a mechanistic or empirical basis. ECOSAR has a training set for each QSAR. For half of the structural fragments the number of chemicals in the training set is >4. Based on structural fragments and log Kow, ECOSAR uses linear regression to predict ecotoxicity. Validating ECOSAR for three 'valid' classes results in predictivity of > or = 64%. BIOWIN uses (non-)linear regressions to predict the probability of biodegradability based on fragments and molecular weight. It has a large training set and predicts non-ready biodegradability well. DEREK for Windows predictions are supported by a mechanistic rationale and literature references. The structural alerts in this program have been developed with a training set of positive and negative toxicity data. However, to support the prediction only a limited number of chemicals in the training set is presented to the user. DEREK for Windows predicts effects by 'if-then' reasoning. The program predicts best for mutagenicity and carcinogenicity. Each structural fragment in ECOSAR and DEREK for Windows needs to be evaluated and validated separately.

External validation of EPIWIN biodegradation models.

The BIOWIN biodegradation models were evaluated for their suitability for regulatory purposes. BIOWIN includes the linear and non-linear BIODEG and MITI models for estimating the probability of rapid aerobic biodegradation and an expert survey model for primary and ultimate biodegradation estimation. Experimental biodegradation data for 110 newly notified substances were compared with the estimations of the different models. The models were applied separately and in combinations to determine which model(s) showed the best performance. The results of this study were compared with the results of other validation studies and other biodegradation models. The BIOWIN models predict not-readily biodegradable substances with high accuracy in contrast to ready biodegradability. In view of the high environmental concern of persistent chemicals and in view of the large number of not-readily biodegradable chemicals compared to the readily ones, a model is preferred that gives a minimum of false positives without a corresponding high percentage false negatives. A combination of the BIOWIN models (BIOWIN2 or BIOWIN6) showed the highest predictive value for not-readily biodegradability. However, the highest score for overall predictivity with lowest percentage false predictions was achieved by applying BIOWIN3 (pass level 2.75) and BIOWIN6.

(Q)SARs: gatekeepers against risk on chemicals?

ECOSAR and DEREKfW predictions for the (eco)toxicological effects of circa 70 substances were compared with experimental data for risk assessment purposes. These and other (quantitative) structure-activity relationships ((Q)SARs) programs will play an important role in future chemical policies, such as in the European Union and The Netherlands, to reduce animal testing and costs and to speed up the number of risk assessments for hazardous chemicals. The two programs, ECOSAR and DEREKfW, were selected because they are easy to use and transparent in their predictions. They predict to which chemical class a substance belongs and also predict some (eco)toxicological properties. ECOSAR categorised 87% of the chemicals correctly in chemical classes. With regard to predicting ecotoxicity, criteria were drawn up for the reliability of the QSARs provided by ECOSAR. Application of these criteria had the result that half of the regression lines from ECOSAR were considered unreliable beforehand. It turned out, however, that the "unreliable" regression lines predicted similar accurately as the "reliable" lines, although much less chemicals were available for validating the "unreliable" QSARs. The overall accurate prediction of toxicity by ECOSAR was 67%. DEREKfW categorised 90% of the chemicals correctly in chemical classes, while 10% of the structural fragments needed a more detailed description. The accuracy of prediction was around 60% for sensitisation, 75% for genotoxicity and carcinogenicity for a limited number of chemicals. Irritation and reproductive toxicity were predicted poorly. Finally, it should be stressed that regulators and industries need to agree on the acceptability criteria relating to false negative and false positive (Q)SAR predictions. This to prevent unnecessary animal testing when regulators do not sufficiently rely on (Q)SAR predictions or to prevent too much faith in (Q)SAR predictions which will then may cause an insufficient protection of man and the environment. Therefore, if the regulatory trend is that (Q)SARs have to be applied more and more systematically in the risk assessment process, their validity and the available tools have to be explored further.

Global government applications of analogues, SARs and QSARs to predict aquatic toxicity, chemical or physical properties, environmental fate parameters and health effects of organic chemicals.

Faced with the need to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals in the absence of experimental data, several Government organizations have been applying analogues, Structure Activity Relationships (SARs) and Quantitative Structure Activity Relationships (QSARs) to develop those predictions. To establish some benchmarks for monitoring future increases in applications of analogues, SARs and QSARs by global Government organizations, this paper describes the current applications of analogues, SARs and QSARs by Australian, Canadian, Danish, European, German, Japanese, Netherlands, and United States Government organizations to predict physical and chemical properties, environmental fate, ecological effects and health effects of organic chemicals.

Exercise performance in patients with end-stage heart failure after implantation of a left ventricular assist device and after heart transplantation: an outlook for permanent assisting?

OBJECTIVES: We sought to study exercise capacity at different points in time after left ventricular assist device (LVAD) implantation and subsequent heart transplantation (HTx). BACKGROUND: The lack of donor organs warrants alternatives for transplantation. METHODS: Repeat treadmill testing with respiratory gas analysis was performed in 15 men with a LVAD. Four groups of data are presented. In group A (n = 10), the exercise capacities at 8 weeks and 12 weeks after LVAD implantation were compared. In group B (n = 15), the data at 12 weeks are presented in more detail. In group C (n = 9), sequential analysis of exercise capacity was performed at 12 weeks after LVAD implantation and at 12 weeks and one year after HTx. In group D, exercise performance one year after HTx in patients with (n = 10) and without (n = 20) a previous assist device was compared. RESULTS: In group A, peak oxygen consumption (Vo2) increased from 21.3+/-3.8 to 24.2+/-4.8 ml/kg body weight per min (p < 0.003), accompanied by a decrease in peak minute ventilation/ carbon dioxide production (VE/Vco2) (39.4+/-10.1 to 36.3+/-8.2; p < 0.03). In group B, peak Vo2 12 weeks after LVAD implantation was 23.0+/-4.4 ml/kg per min. In group C, levels of peak Vo2 12 weeks after LVAD implantation and 12 weeks and one year after HTx were comparable (22.8+/-5.3, 24.6+/-3.3 and 26.2+/-3.8 ml/kg per min, respectively; p = NS). In group D, there appeared to be no difference in percent predicted peak Vo2 in patients with or without a previous LVAD (68+/-13% vs. 74+/-15%; p < 0.37), although, because of the small numbers, the power of this comparison is limited (0.45 to detect a difference of 10%). CONCLUSIONS: Exercise capacity in patients with a LVAD increases over time; 12 weeks after LVAD implantation, Vo2 is comparable to that at 12 weeks and one year after HTx. Previous LVAD implantation does not seem to adversely affect exercise capacity after HTx.