Evaluation of the ventricular assist device programme in the UK.

OBJECTIVES: To summarise the relevant clinical effectiveness and cost-effectiveness literature, to collect data on survival, transplantation rates, health-related quality of life (HRQoL) and resource use for ventricular assist device (VAD) and non-VAD transplant candidates in the UK, and to construct cost-effectiveness and cost-utility models of VADs in a UK context. Also to investigate the factors that drive costs and survival. DESIGN: A comprehensive systematic review was carried out. Data were collected from April 2002 to December 2004, with follow-up to March 2005. Cost-effectiveness and cost-utility models of VAD devices were developed based on UK activity and outcomes collected from April 2002 to March 2005. SETTING: National Specialist Commissioning Advisory Group funded VAD implantation was carried out at the Freeman, Harefield and Papworth transplant centres in the UK. PARTICIPANTS: Seventy patients were implanted with a VAD as a bridge to transplantation between April 2002 and December 2004. Non-VAD-supported transplant candidates (n = 250), listed at the three centres between April 2002 and December 2004, were divided into an inotrope-dependent group (n = 71) and a non-inotrope-dependent group (n = 179). Although patients in the inotrope-dependent group were closest to the VAD group they were less sick. The last group comprised a hypothetical worst case scenario, which assumed that all VAD patients would die in the intensive care unit (ICU) within 1 month without VAD technology. INTERVENTIONS: Patients were included who were implanted with a VAD designed for circulatory support for more than 30 days, with intention to bridge to transplantation. A multistate model of VAD and transplant activity was constructed; this was populated by data from the UK. MAIN OUTCOME MEASURES: Survival from VAD implant or from transplant listing for non-VAD patients to 31 March 2005. Serious adverse events and quality of life measures were used. Cognitive functioning was also assessed. Utility weights were derived from EuroQoL responses to estimate quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) were defined as the additional cost of VADs divided by additional QALYs. Time-horizons were 3 years, 10 years and the lifetime of the patients. RESULTS: Of 70 VAD patients, 30 (43%) died pretransplant, 31 (44%) underwent transplantation, and four (6%) recovered and had the VAD removed. Five patients (7%) were still supported for median of 279 days at the end of March 2005. Successful bridge-to-transplantation/recovery rates were consistent with published rates. Survival from VAD implantation was 74% at 30 days and 52% at 12 months. There were 320 non-fatal adverse events in 62 patients during 300 months of VAD support, mostly in the first month after implantation. Commonly observed events were bleeding, infection and respiratory dysfunction. Twenty-nine (41%) patients were discharged from hospital with a VAD. The 1-year survival post-transplantation was 84%. For the inotrope-dependent and non-inotrope-dependent transplant candidates, death rates while listed were 10% and 8% and the median waiting times were 16 and 87 days, respectively. For transplant recipients, 1-year survival was 85% and 84%, respectively. Both VAD and non-VAD patients demonstrated similar significant improvements in their New York Heart Association class after transplantation. All patients had poor EQ-5D pretransplantation; after transplantation the groups had similar EQ-5D of 0.76 irrespective of time after surgery. HRQoL was poor in the first month for VAD patients but better for those who waited longer in all groups. VAD patients reported more problems with sleep and rest and with ambulation in the first month. Symptom scores were similar in all groups pretransplant. After transplantation all groups showed a marked and similar improvement in physical and psychosocial function. Mean VAD implant cost, including device, was pound 63,830, with costs of VAD support for survivors of pound 21,696 in month 1 and pound 11,312 in month 2. Main cost drivers were device itself, staffing, ICU stay, hospital stay and events such as bleeding, stroke and infection. For the base case, extrapolating over the lifetime of the patients the mean cost for a VAD patient was pound 173,841, with mean survival of 5.63 years and mean QALYs of 3.27. Corresponding costs for inotrope-dependent patients were pound 130,905, with mean survival 8.62 years and mean QALYs 4.99. Since inotrope-dependent patients had lower costs and higher QALYs than VAD patients, this group is said to be dominant. Non-inotrope-dependent transplant candidates had similar survival rates to those on inotropes but lower costs, also dominant. Compared with the worst case scenario the mean lifetime ICER for VADs was pound 49,384 per QALY. In a range of sensitivity analyses this ranged from pound 35,121 if the device cost was zero to pound 49,384. Since neither inotrope-dependent transplant candidates nor the worst case scenario were considered fair controls the assumption was investigated that, without VAD technology, there would be a mixture of these situations. For mixtures considered the ICER for VADs ranged from pound 79,212 per QALY to the non-VAD group being both cheaper and more effective. CONCLUSIONS: There are insufficient data from either published studies or the current study to construct a fair comparison group for VADs. Overall survival of 52% is an excellent clinical achievement for those young patients with rapidly failing hearts. However, if the worst case scenario were plausible, and one could reliably extrapolate results to the lifetime of the patients, VADs would not be cost-effective at traditional thresholds. Further randomised controlled trials are required, using current second generation devices or subsequent devices and conducted in the UK.

A review of the evidence on the effects and costs of implantable cardioverter defibrillator therapy in different patient groups, and modelling of cost-effectiveness and cost-utility for these groups in a UK context.

OBJECTIVES: To update the systematic review evidence on the effectiveness, health-related quality of life (HRQoL) and cost-effectiveness of implantable cardioverter defibrillators (ICDs); compilation of new data on the service provision in the UK; and on the clinical characteristics, survival, quality of life and costs of ICD patients in the UK, and a new cost-effectiveness model using both international RCT and UK-specific data. DATA SOURCES: Electronic databases searched from November 1999 to March 2003, this was supplemented by a systematic review of research published during 2003-5. Survey data. REVIEW METHODS: Studies were selected and assessed. A survey of ICD centres was carried out. Basic data were obtained from two major implanting centres including 535 patients (approximately 10% of overall UK activity) implanted between 1991 and 2002, and retrieval of fuller data, on patient characteristics, management and resource use, from patient notes for a sample of 426 patients was attempted. A cross-sectional survey collected HRQoL data (using the Nottingham Health Profile, Short Form 36, Hospital Anxiety and Depression questionnaire, EuroQoL 5 Dimensions and disease-specific questions) on a sample of 229 patients. A Markov model combined UK patient data with data from published randomised controlled trials (RCTs) to estimate incremental costs per life-year or quality-adjusted life-year (QALY) gained. RESULTS: None of the economic analyses in the studies found could be directly applied to the UK. The multiple sources of routine data available (including the national ICD database) provide an imperfect picture of the need for and use of ICDs. Implantation rates have been rising to a rate of around 20 per million population. Mean age is increasing and most ICDs are implanted into men aged 45-74 years. There is significant geographical variation. A survey of 41 UK centres provided additional evidence, particularly of variation in level of activity and resourcing. Most detailed data were obtained for 380 patients (89%). The postal survey produced a 73% response rate. Demographic characteristics of these patients were similar to ICD recipients in the UK as a whole and patients included in secondary prevention RCTs. Mean actuarial survival at 1, 3 and 5 years was 92%, 86% and 71%, respectively. Patient age at implantation and functional status significantly affected survival. Levels of most of the HRQoL measures were lower than for a UK general population. There was no evidence of a change with time from implantation. Patients who had suffered ICD shocks had significantly poorer HRQoL. Most patients nevertheless expressed a high level of satisfaction with ICD therapy. Mean initial costs of implantation showed little variation between centres (23,300 pounds versus 22,100 pounds) or between earlier and more recent implants. There appeared to be greater variation between patients presenting along different pathways. Postdischarge costs (tests, medications and follow-up consultations) and costs of additional hospitalisations were also calculated. Using the Markov model it was found that over a 20-year horizon, mean discounted incremental costs were 70,900 pounds (35,000-142,400 pounds). Mean discounted gain was 1.24 years (0.29-2.32) or 0.93 QALYs. Cost-effectiveness was most favourable for men aged over 70 years with a left ventricular ejection fraction (LVEF) below 35%. If the treatment effect were to continue, then the cost per life-year over a lifetime might fall to around 32,000 pounds. Five RCTs of ICDs, a meta-analysis and, a cost-effectiveness analysis of ICDs used in primary prevention, and a meta-analysis of ICDs in patients with non-ischaemic cardiomyopathy have been published recently. These trials provide confirmation of survival benefit of ICDs used in primary prevention in both ischaemic and non-ischaemic cardiomyopathy patients. Costs per QALY ranged from US$34,000 in older trials to controls being both less expensive and more effective (CABG Patch, DINAMIT). More recent trials estimated cost per QALY between $50,300 and $70,200. The inconsistency in evidence for a HRQoL benefit has not been resolved and further work on risk stratification is necessary. CONCLUSIONS: The evidence of short- to medium-term patient benefit from ICDs is strong but cost-effectiveness modelling indicates that the extent of that benefit is probably not sufficient to make the technology cost-effective as used currently in the UK. One reason is the high rates of postimplantation hospitalisation. Better patient targeting and efforts to reduce the need for such hospitalisation may improve cost-effectiveness. Further cost-effectiveness modelling, underpinned by an improved ICD database with reliable long-term follow-up, is required. The absence of a robust measure of the incidence of sudden cardiac death is noted and this may be an area where further organisational changes with improved data collection would help.

A randomised controlled crossover trial of nurse practitioner versus doctor led outpatient care in a bronchiectasis clinic.

BACKGROUND: With the decrease in junior doctor hours, the advent of specialist registrars, and the availability of highly trained and experienced nursing personnel, the service needs of patients with chronic respiratory diseases attending routine outpatient clinics may be better provided by appropriately trained nurse practitioners. METHODS: A randomised controlled crossover trial was used to compare nurse practitioner led care with doctor led care in a bronchiectasis outpatient clinic. Eighty patients were recruited and randomised to receive 1 year of nurse led care and 1 year of doctor led care in random order. Patients were followed up for 2 years to ensure patient safety and acceptability and to assess differences in lung function. Outcome measures were forced expiratory volume in 1 second (FEV(1)), 12 minute walk test, health related quality of life, and resource use. RESULTS: The mean difference in FEV(1) was 0.2% predicted (95% confidence interval -1.6 to 2.0%, p=0.83). There were no significant differences in the other clinical or health related quality of life measures. Nurse led care resulted in significantly increased resource use compared with doctor led care (mean difference pound 1497, 95% confidence interval pound 688 to pound 2674, p<0.001), a large part of which resulted from the number and duration of hospital admissions. The mean difference in resource use was greater in the first year ( pound 2625) than in the second year ( pound 411). CONCLUSIONS: Nurse practitioner led care for stable patients within a chronic chest clinic is safe and is as effective as doctor led care, but may use more resources.

The influence of ethnicity on thermosensitivity during cold water immersion.

PURPOSE: This investigation evaluated the influence of ethnicity, Caucasian (CAU) vs. African American (AA), on thermosensitivity and metabolic heat production (HP) during cold water immersion (20 degrees C) in 15 CAU (22.7 +/- 2.7 yr) vs. 7 AA (21.7 +/- 2.7 yr) males. METHODS: Following a 20-min baseline period (BASE), subjects were immersed in 20 degrees C water until esophageal temperature (Tes) reached 36.5 degrees C or for a maximum pre-occlusion (Pre-OCC) time of 40 min. Arm and thigh cuffs were then inflated to 180 and 220 mm Hg, respectively, for 10 min (OCC). Following release of the inflated cuffs (Post-OCC), the slope of the relationship between the decrease in Tes and the increase in HP was used to define thermosensitivity (beta). RESULTS: ANOVA revealed no significant difference in thermosensitivity between CAU and AA (CAU = 3.56 +/- 1.54 vs. AA = 2.43 +/- 1.58 W.kg(-1). degrees C(-1)). No significant differences (p > 0.05) were found for Tsk (CAU = 24.2 +/- 1.1 vs. AA = 25.1 +/- 1.1 degrees C) or HP (p > 0.05; CAU = 2.5 +/- 0.8 vs. AA = 36.5 +/- 1.8 W.kg(-1)). However, a significant (p < 0.05) main effect for ethnicity for Tes was observed (CAU = 36.7 +/- 1.8 vs. AA = 36.5 +/- 1.8 degrees C). CONCLUSION: These data suggest, despite a differential response in Tes between AA and CAU groups, the beta of HP during cold water immersion is similar between CAU and AA. Therefore, these data demonstrate that when faced with a cold challenge, there is a similar response in HP between CAU and AA that is accompanied by a differential response in Tes.

A UK trial-based cost--utility analysis of transmyocardial laser revascularization compared to continued medical therapy for treatment of refractory angina pectoris.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) is used to treat patients with refractory angina considered unsuitable for conventional forms of revascularization. Using patient specific data from a single centre UK randomised-controlled trial, we aimed to determine whether, from a UK National Health Service (NHS) perspective, TMLR plus standard medical management is cost-effective when compared with standard medical management alone. METHODS: One hundred and eighty-eight patients assessed as having refractory angina, and not suitable for conventional forms of revascularization were randomized to receive TMLR and medical management (94) or medical management alone (94). Costs to the UK NHS of TMLR (where appropriate), and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomization, were collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was combined with 12-month survival data to generate quality adjusted life years (QALYs). RESULTS: The mean cost per patient over the year from hospitalization for TMLR was 11,470 pounds sterling and for medical management alone was 2586 pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268). This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis of stochastic uncertainty and of sensitivity to gross changes in key parameters consistently produces very high costs per QALY. CONCLUSIONS: The policy implications are clear: for such patients TMLR is an inefficient use of UK health service resources. This conclusion would not be changed by considerable improvements in effectiveness or reductions in cost.

A model for analyzing the cost of the main clinical events after lung transplantation.

BACKGROUND: The aim of this project was to model clinically important events experienced by lung transplant patients (from the day after transplant to 5 years or death) and costs associated with these events, and to assess the economic impact of different immunosuppression therapies. METHODS: The population comprised 356 lung transplant patients (223 heart-lung, 102 single lung and 31 double lung) transplanted between April 1984 and December 1997. All patients received a cyclosporine-based triple-immunosuppression protocol. We designed a Markov model that included 3 time periods (0 to 6, 7 to 12, and 13 to 60 months), 5 clinical states (well, acute rejection, cytomegalovirus infection, non-cytomegalovirus infection and bronchiolitis obliterans syndrome), and death. For the well state, cost elements were immunosuppression, prophylaxis, and routine clinic visits. For all other states, cost elements were diagnosis, treatment, and bed days/visits. We excluded costs of the procedure. RESULTS: The monthly costs associated with the well state decreased over time, from pound sterlings 1,778 ($2,658) in the first 6 months to pound sterlings 503 ($752) in months 7 to 12 and pound sterlings 350 ($523) after the first 12 months. The cost per event of the acute states remained reasonably constant over the 3 periods: pound sterlings 1,850 ($2,766) for rejection, pound sterlings 3,380 ($5,053) for cytomegalovirus, and pound sterlings 2,790 ($4,171) for other infections. The average cost per patient, discounted at 6%, over 5 years was pound sterlings 35,429 ($52,966) (95% range, pound1,435 [$2,145] to pound67,079 [$100,283]). This estimate is most sensitive to changes in immunosuppression. Substituting tacrolimus for cyclosporine increased 5-year costs by 5%; substituting mycophenolate mofetil for azathioprine increased 5-year costs by 26%. CONCLUSIONS: This model is valuable in estimating the effect of new immunosuppression agents on the costs of follow-up care.

Thermal sensation and substrate utilization differs among low- and high-fat women exposed to 17 degrees C water.

OBJECTIVE: Thermal sensation and the physiological responses of women (follicular phase) exposed to 17 degrees C immersion for 120 minutes were investigated. METHODS: The subjects were divided into 2 groups by percent body fat (low fat [LF] = 21% +/- 2% [mean +/- SD] vs high fat [HF] = 30% +/- 3%). A 2-way analysis of variance was used to determine differences between the groups in metabolism, metabolism derived from carbohydrate, metabolism derived from fat, blood glucose, rectal temperature, skin temperature, and thermal sensation. RESULTS: As anticipated, pooled metabolism increased across the 120-minute immersion. Metabolism derived from carbohydrate was significantly higher in the LF than in the HF group and increased across time. Blood glucose decreased significantly across time, yet there was no group difference, suggesting that the LF group may have utilized a greater proportion of intramuscular glycogen. The HF group demonstrated a higher rectal temperature compared to their LF counterparts. Overall, rectal temperature demonstrated a group x time interaction as immersion continued. However, rectal temperature for all subjects remained above 35 degrees C. Surprisingly, the HF group perceived significantly greater thermal discomfort than did their LF counterparts. CONCLUSIONS: Since intramuscular glycogen utilization is associated with shivering thermogenesis, the suspected greater utilization of this fuel by the LF group may have contributed to less thermal discomfort than in the HF group. However, since glycogen utilization was not directly measured, this speculation cannot be validated. It is also possible that the modified thermal sensation scale we used may not be an adequate marker of thermal discomfort in females with a high percentage of body fat (28% to 35%) exposed to cold water immersion.

Influence of gender and menstrual cycle on a cold air tolerance test and its relationship to thermosensitivity.

This investigation evaluated the influence of gender and phase of menstrual cycle [follicular (FOL): Days 2-6) and luteal (LUT: Days 19-24)] on a cold air tolerance test (CATT: 90-min of exposure to 5 degrees C air) in 8 females (22.7 +/- 3.0 yr) and 15 males (22.3 +/- 2.9 yr). In addition, central thermosensitivity (beta; W x kg(-1) x degrees C(-1) [i.e., the slope of the relationship between the decrease in esophageal temperature (Tes) and the increase in heat production (HP)], gathered during a separate water trial in 20 degrees C water, was correlated to the change (delta) in Tes and HP across the 90 min of resting exposure during the CATT. Analysis of variance revealed no significant differences between phase of menstrual cycle or gender for HP, mean skin temperature (Tsk), and insulation; however, a main effect for time for these parameters was demonstrated. Despite these similarities, Tes differed (P < 0.05) between males and females. Additionally, no relationship was found between beta and deltaHP and deltaTes in the males and females. Also, there was no relationship between beta and thermoregulation during the CATT in these subjects. These data suggest that menstrual cycle phase did not cause a differential response in Tes, Tsk, and HP during a CATT. Furthermore, women maintained a higher Tes than men during the CATT despite similarities in HP and Tsk.

The influence of gender and menstrual phase on thermosensitivity during cold water immersion.

BACKGROUND: This investigation evaluated the influence of gender and phase of menstrual cycle [follicular (FOL: days 2-6) and luteal (LUT: days 19-24) phases] on thermosensitivity and metabolic heat production (HP) during cold water immersion (20 degrees C) in 10 females (22.4 +/- 2.8 yr) and 16 males (22.4 +/- 2.9 yr). METHODS: Following a 20-min baseline period (BASE), subjects were immersed until esophageal temperature (Tes) reached 36.5 degrees C or for a maximum pre-occlusion (Pre-OCC) time of 40 min. An arm and thigh cuff were then inflated to 180 and 220 mmHg, respectively, for 10 min (OCC). Following release of the inflated cuffs (Post-OCC), the slope (beta) of the relationship between the decrease in Tes and the increase in HP was used to quantify thermosensitivity. RESULTS: ANOVA revealed no significant difference in thermosensitivity between phases of the menstrual cycle or between men and women (FOL = -2.76, LUT = -3.05, Males = -3.24 W x kg(-1) x degrees C(-1)). A significant (p < 0.05) main effect for gender for HP, and a significant (p < 0.05) main effect for menstrual phase for mean skin temperature (Tsk) were observed. CONCLUSIONS: These data suggest, despite gender differences in HP, that the thermosensitivity of HP during cold water immersion is similar between males and females and is not influenced by menstrual cycle phase. Therefore, these data indicate that when faced with a cold challenge, women respond similarly to men in both phases of their menstrual cycle.

The effects of gender and menstrual phase on carbohydrate utilization during acute cold exposure.

OBJECTIVE: The purpose of this study was to evaluate the effects of gender and menstrual cycle on the percent of carbohydrate (CHO) utilized during cold water immersion (20 degrees C). Previous research has suggested that males and females utilize CHO differently during submaximal exercise. This study examined whether this differential response is replicated during a submaximal elevation in metabolism, as demonstrated during thermogenesis (i.e., shivering during acute cold exposure). METHODS: Male and female subjects between the ages of 18 and 30 years were recruited for this study. Female subjects underwent the experimental trial once during the follicular phase and once during the luteal phase of their menstrual cycle. Subjects were immersed to the first thoracic vertebra until esophageal temperature reached 36.5 degrees C or for a maximum preocclusion period of 40 minutes. Peripheral temperature homeostasis via cuff occlusion (right arm and left leg) took place for 10 minutes, after which the pressure cuffs were released (postocclusion) and the subjects remained in the water for an additional 10 minutes. The following variables were measured: respiratory exchange ratio, percent of CHO utilization, and oxygen consumption (Vo2). RESULTS: Analysis of variance demonstrated no significant difference between genders or phases of the menstrual cycle in respiratory exchange ratio, percent CHO utilization, or Vo2 during cold water immersion. A significant difference was observed between men and women for absolute Vo2. CONCLUSIONS: These data suggest that although men and women differ with respect to absolute aerobic metabolism, this distinction does not cause a differential response with respect to substrate utilization during acute cold exposure.

Demonstration of a foraging advantage for trichromatic marmosets (Callithrix geoffroyi) dependent on food colour.

It has been suggested that the major advantage of trichromatic over dichromatic colour vision in primates is enhanced detection of red/yellow food items such as fruit against the dappled foliage of the forest. This hypothesis was tested by comparing the foraging ability of dichromatic and trichromatic Geoffroy's marmosets (Callithrix geoffroyi) for orange- and green-coloured cereal balls (Kix) in a naturalized captive setting. Trichromatic marmosets found a significantly greater number of orange, but not green, Kix than dichromatic marmosets when the food items were scattered on the floor of the cage (at a potential detection distance of up to 6 m from the animals). Under these conditions, trichromats but not dichromats found significantly more orange than green Kix, an effect that was also evident when separately examining the data from the end of the trials, when the least conspicuous Kix were left. In contrast, no significant differences among trichromats and dichromats were seen when the Kix were placed in trays among green wood shavings (detection distance < 0.5 m). These results support an advantage for trichromats in detecting orange-coloured food items against foliage, and also suggest that this advantage may be less important at shorter distances. If such a foraging advantage for trichromats is present in the wild it might be sufficient to maintain the colour vision polymorphism seen in the majority of New World monkeys.

Thermal and metabolic responses of high and low fat women to cold water immersion.

BACKGROUND: At rest during cold exposure, the amount of body fat plays an important role in the maintenance of core temperature. High fat (HF) individuals would therefore have an advantage as compared with their low fat (LF) counterparts. Since females usually have a higher amount of body fat than males they are expected to maintain core temperature at a lower energy cost. METHODS: The purpose of the present investigation was to dichotomize female subjects by percent fat (LF = 20.5 +/- 2%, n = 6 vs. HF = 30 +/- 3%, n = 6) to elucidate the thermal and metabolic responses during acute exposure to 17 degrees C water for 120 min. The following variables were measured: rectal temperature (Tre; degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)), and tissue insulation (I; degrees C x m2 x W(-1)). The experiment-wise error rate was set a priori at p = 0.05. RESULTS: Unexpectedly, only one of the variables demonstrated a main effect for fat (p < 0.05). Tre demonstrated a significant (p < 0.05) group by time interaction. However, Tsk and I demonstrated a main effect for time (p < 0.05). While VO2 demonstrated an increase across time, these changes were non-significant (p > 0.05). It appears that the HF group demonstrated a similar thermal (I and Tsk) and metabolic (VO2) response as compared with the LF counterparts. However, the LF groups maintained a lower Tre as compared with the HF subjects. Perhaps leaner subjects or colder water temperatures would elucidate the value of body fat in females, and demonstrate a differential response with respect to females varying in percent body fat.

Thermal and metabolic responses of women with high fat versus low fat body composition during exposure to 5 and 27 degrees C for 120 min.

BACKGROUND: Men with high fat body composition maintain higher core temperatures, and lower aerobic metabolic rates than their low fat counterparts thus, verifying the insulatory benefit of body fat. Females, on average have more body fat and less muscle mass than males, and may maintain rectal temperature (Tre) at a lower energy cost. METHODS: The present investigation dichotomized female subjects by percent fat (low fat; n = 3, LF = 19.2+/-3% vs. high fat; n = 4 HF: 29.9+/-3%) to elucidate the thermal and metabolic responses during acute exposure to 5 and 27 degrees C air for 120 min. An ANOVA was used to examine the following: Tre (degrees C), mean skin temperature (Tsk; degrees C), oxygen consumption (VO2; ml x kg(-1) x min(-1)) and tissue insulation (I; degrees C x m2 x W(-1)). For Tre, a significant fat x time interaction (p < 0.05) was demonstrated at both 5 and 27 degrees C, whereby Tre tended to be lower in the LF group than the HF group. VO2 at 5 degrees C demonstrated a main effect for time only. For I, a main effect for time was noted at 5 degrees C. Also for I, a trend (p = 0.06) toward a main effect of fat during exposure to 5 degrees C was noted while at 27 degrees C a main effect (p < 0.05) was demonstrated. RESULTS: From this data it appears that under these conditions, the HF group demonstrated higher Tre and I values than their LF counterparts that was not accompanied with a differential response with respect to aerobic metabolic rate. Thus, the impact of body composition on energy expenditure to maintain Tre differs between LF and HF males and females.

Prospective study of health related quality of life before and after coronary artery bypass grafting: outcome at five years.

OBJECTIVE: To determine the long term health related quality of life of coronary artery bypass graft patients, to look at changes between one and five years after surgery, and to examine the ability of preoperative variables to predict longer term outcome. DESIGN: Nottingham health profile (NHP) was used to assess patients at five years compared to results obtained at one year. PATIENTS: 100 male patients aged < 60 years at time of surgery; 77 had three vessel disease and 84 received three or more saphenous vein grafts. RESULTS: In comparing the five year results with those at one year, lower mean scores, indicating slight improvements, were seen in the NHP dimensions of pain, sleep, social isolation, and emotional reactions, whereas signs of deterioration were noted in the physical mobility and energy scores. Chest pain was experienced by 34 of 84 patients at five years compared with 17 of 89 patients at one year. The proportion of patients who were unrestricted in their activities ranged from 61-70% at five years compared with 82-88% at one year. Absence of dyspnoea before surgery, indicating relatively good left ventricular function, was a predictor of good outcome at both one and five years. CONCLUSIONS: Evidence of deterioration in physical function is compatible with expected decline in graft patency; specific rather than generic measures were most sensitive to this change.

The transmyocardial laser revascularization international registry report.

AIMS: This report aimed to provide an analysis of the data submitted from Europe and Asia on transmyocardial laser revascularization. METHODS AND RESULTS: Prospective data was recorded on 967 patients with intractable angina not amenable to conventional revascularization in 21 European and Asian centres performing transmyocardial laser revascularization using the PLC Medical Systems CO2 laser. Patient characteristics, operative details and early complications following transmyocardial laser revascularization were recorded. The in-hospital death rate was 9.7% (95% confidence interval 7.8% to 11.6%). Other early complications were consistent with similar cardiothoracic surgical procedures. There was a decrease of two or more Canadian Cardiovascular Score angina classes in 47.3%, 45.4% and 34.0% of survivors at 3, 6 and 12 months follow-up, respectively (P=0.001 for each). Treadmill exercise time increased by 42 s at 3 months (P=0.008), 1 min 43 s at 6 months (P<0.001) and 1 min 50 s at 12 months (P<0.001) against pre-operative times of 6 min. CONCLUSION: Uncontrolled registry data suggest that transmyocardial laser revascularization may lead to a decrease in angina and improved exercise tolerance. It does, however, have a risk of peri-operative morbidity and mortality. Definitive results from randomized controlled trials are awaited.

Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.

BACKGROUND: Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management. METHODS: 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk. FINDINGS: Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001). INTERPRETATION: Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.