Size matching in lung transplantation using predicted total lung capacity.

Height is used in allocation of donor lungs as an indirect estimate of thoracic size. Total lung capacity (TLC), determined by both height and sex, could be a more accurate functional estimation of thoracic size. Size-matching criteria based on height versus predicted TLC was retrospectively evaluated, and, furthermore, whether a TLC mismatch was related to clinical and functional complications. The ratio of donor and recipient height, as well as the ratio of predicted TLC in donors and recipients, were calculated in 80 patients after bilateral lung transplantation. Complications evaluated included persistent atelectasis, persistent pneumothorax and increased number of days in intensive care, occurrence of bronchiolitis obliterans syndrome and limitation of exercise capacity. Median height donor/recipient ratio was 1.01 (0.93-1.12). Median predicted TLC donor/recipient ratio was 1.01 (with a clearly broader range 0.72-1.41). Neither sex mismatch nor TLC mismatch were related to clinical or functional complications. Allocation of donor lungs based upon height alone leads to a substantial mismatch in total lung capacity caused by sex mismatch. The absence of complications suggests that a greater height donor/recipient discrepancy can be accepted for allocation than previously assumed.

Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches.

BACKGROUND: The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain. METHODS: A retrospective analysis of 102 consecutive primary lung transplants was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteristics (age, sex, prior diagnosis), the number of HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus serologic concordance, number of acute rejections, and time to first rejection. Variables carrying significance in a univariate analysis were subjected to a proportional hazard regression analysis. RESULTS: In the multivariate analysis, an increased number of acute rejections correlated positively with decreased graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P < 0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An increased time to rejection correlated positively with reduced graft survival (RR = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR = 1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19-0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95% CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P = 0.017). CONCLUSIONS: HLA-DR mismatching appears to be a risk factor for the development of BOS and graft loss. Improved outcome after lung transplantation might be achieved with prospective matching for HLA-DR. Alternatively, the amount and type of immunosuppressive drugs may be guided by the degree of HLA-DR (mis)matching.

Quality of life before and after lung transplantation in patients with emphysema versus other indications.

Whether lung transplantation improves Health-related Quality of Life in patients with emphysema and other end-stage lung diseases before and after lung transplantation was examined. Between 1992 and 1999, 23 patients with emphysema and 19 patients with other indications completed self-administered questionnaires before lung transplantation, and at 4, 7, 13, and 25 mo. after transplantation. The questionnaire included the Nottingham Health Profile, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-being, the self-report Karnofsky Index, and four respiratory-specific questions. Neither before nor after transplantation were significant differences found on most dimensions of Health-related Quality of Life between patients with emphysema and other indications. Before transplantation, both groups report major restrictions on the dimensions Energy and Mobility of the Nottingham Health Profile, low experienced well-being, depressive symptoms, and high dyspnea. About 4 mo. after transplantation, most Health-related Quality of Life measures improved significantly in both groups. These improvements were maintained in the following 21 mo.

Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life.

The present study was undertaken to assess the relationship between health-related quality of life (HRQOL) and bronchiolitis obliterans syndrome (BOS), as both represent important parameters of outcome after lung transplantation. HRQOL was measured both cross-sectionally and longitudinally by standardized patient self-administered questionnaires, including the Nottingham Health Profile, the State-trait Anxiety Inventory, the Zung Self-Rating Depression Scale, and the Index of Well-Being. Data were collected at 4 and 7 mo, and every 6 mo afterwards for as long as 49 mo post-transplantation. The number of patients who completed the questionnaires varied from 72 at 4 mo, to 27 at 49 mo after transplantation. Cross-sectionally, the patients with BOS reported persistently statistically significantly more restrictions on the dimensions energy and physical mobility of the Nottingham Health Profile compared with patients without BOS. Other domains, i.e., pain, sleep, social interaction, and emotional reactions, were not affected. Additionally, patients with BOS reported statistically significantly more depressive symptoms and anxiety 1 and 2 yr after transplantation. Results from the longitudinal analysis support these findings, although no change in depressive symptoms could be found after onset of BOS. This study suggests that all lung transplant recipients improve in HRQOL. The development of BOS, however, is associated with a significantly reduced HRQOL.

Does lung transplantation prolong life? A comparison of survival with and without transplantation.

BACKGROUND: Because of the assumed beneficial effect of lung transplantation on survival, controlled trials to assess the therapeutic benefit of lung transplantation are considered to be unethical. Therefore other methods must be used to provide control data. In this study the effect of lung transplantation on survival for patients with end-stage pulmonary disease was analyzed, with waiting list survival rates used as control data. METHODS: The analysis was based on 157 consecutive patients who were put on the waiting list of the Dutch lung transplantation program during the period November 1990 to January 31, 1996, of whom 76 underwent transplantation. Following the principles of control group estimation as set out in the context of heart transplantation, a stepwise approach was used to arrive at a multivariate time-dependent Cox regression model. The following prognostic variables were included in the analyses: age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis. RESULTS: The 1- and 2-year waiting list survival rates were 78% and 58%, respectively. The 1- and 2-year transplantation survival rates (i.e., survival from placement on the waiting list, including posttransplantation survival) were 79% and 64%, respectively. The multivariate time-dependent Cox analysis showed that lung transplantation reduced the risk of dying by 55% (95% confidence interval, 3% to 79%). For patients with emphysema the risk of dying was estimated to be 77% lower than for patients with other diagnoses (96% confidence interval, 50% to 89%). CONCLUSIONS: With Cox regression, adjusting for age, forced expiratory volume in 1 second, partial pressure of carbon dioxide, partial pressure of oxygen, and diagnosis, lung transplantation showed a statistically significant effect on survival in selected patients with end-stage pulmonary disease.

[The evaluation of the lung transplantation program at Groningen: survival rate, quality of life, and cost-effectiveness]. / Evaluatie van het groningse longtransplantatieprogramma: overleving, kwaliteit van leven en kosteneffectiviteit.

OBJECTIVE: Assessment of the effectiveness and cost-effectiveness of lung transplantation, and the supply and need of donor lungs in the Netherlands. DESIGN: Prospective and comparative. SETTING: University Hospital Groningen, the Netherlands. METHOD: Costs and effects were compared of the situations with and without a lung transplantation programme. Costs and effects were registered during all phases of this programme (November 1990 to February 1996; 76 patients reached the transplantation phase), and the situation without a programme was judged on pre-transplant evidence. The effect of lung transplantation on survival was assessed by means of a Cox regression model, and in the quality of life study of a longitudinal analysis was applied. The supply and the need of donor lungs were based on several registrations. RESULTS: Lung transplantation led to a significant improvement in survival and quality of life. The average gain in life years and quality adjusted life years (Qalys) were estimated at 4.4 and 5.2, respectively. The average costs per transplanted patient were estimated at Hfl. 670,000 (Hfl. 1 is about 0.5 dollar). The average costs per life year and Qaly gained were estimated at Hfl 153,000 and Hfl. 120,000 (both discounted), respectively. The annual need of donor lungs was estimated at 50-75, the annual supply at 17-27. CONCLUSIONS: Lung transplantation leads to improvement of survival and quality of life. However, it involves considerable costs and the cost-effectiveness is unfavourable compared with other Dutch transplant programmes. Moreover, there is a great discrepancy between the need and supply of donor lungs in the Netherlands.

Technology assessment of the Dutch Lung Transplantation Program.

The costs, effects, and cost-effectiveness of the Dutch Lung Transplantation program were assessed. The results show that lung transplantation is a very costly intervention that improves survival and quality of life. Costs per life-year and per QALY gained were, respectively, US $90,000 and US $71,000.

The effect of lung transplantation on health-related quality of life: a longitudinal study.

STUDY OBJECTIVES: To assess the change in health-related quality of life (HRQL) among Dutch lung transplant patients before and after transplantation. DESIGN: Prospective longitudinal study on HRQL among 24 Dutch lung transplant patients who participated first as transplant candidates, and later as recipients in the study. This study design provides an accurate estimate of the change in HRQL as a result of lung transplantation because there is no confounding between change due to differences in composition between groups of patients at the different points of follow-up and the true change as a result of the transplantation. Patients completed self-administered questionnaires before transplantation, and at 1, 4, 7, 13, and 19 months after transplantation. The main HRQL measures were: the Nottingham health profile (NHP), the State-trait Anxiety Inventory, the Self-rating Depression Scale-Zung, the Karnofsky Performance Index, the index of well-being, and activities of daily living (ADL). SETTING: University Hospital Groningen, the Netherlands. RESULTS: Before transplantation, patients report major restrictions on the dimensions mobility and energy of the NHP, a low level of experienced well-being, and depressive symptoms. In addition, patients experience difficulties in performing ADL and report a low ability to take care of themselves. About 4 months after transplantation, mobility, energy, sleep, ADL dependency level, and dyspnea were particularly positively affected by the lung transplantation. These improvements were maintained in the following 15 months. CONCLUSIONS: Lung transplantation contributes positively to the HRQL of surviving patients over time.

Cost-effectiveness of lung transplantation in The Netherlands: a scenario analysis.

STUDY OBJECTIVES: To calculate cost-effectiveness of scenarios concerning lung transplantation in The Netherlands. DESIGN: Microsimulation model predicting survival, quality of life, and costs with and without transplantation program, based on data of the Dutch lung transplantation program of 1990 to 1995. SETTING: Netherlands, University Hospital Groningen. PATIENTS: Included were 425 patients referred for lung transplantation, of whom 57 underwent transplantation. INTERVENTION: Lung transplantation. RESULTS: For the baseline scenario, the costs per life-year gained are G 194,000 (G=Netherlands guilders) and the costs per quality-adjusted life-year (QALY) gained are G 167,000. Restricting patient inflow ("policy scenario") lowers the costs per life-year gained: G 172,000 (costs per QALY gained: G 144,000). The supply of more donor lungs could reduce the costs per life-year gained to G 159,000 (G 135,000 per QALY gained; G1 =US $0.6, based on exchange rate at the time of the study). CONCLUSIONS: Lung transplantation is an expensive but effective intervention: survival and quality of life improve substantially after transplantation. The costs per life-year gained are relatively high, compared with other interventions and other types of transplantation. Restricting the patient inflow and/or raising donor supply improves cost-effectiveness to some degree. Limiting the extent of inpatient screening or lower future costs of immunosuppressives may slightly improve the cost-effectiveness of the program.

Lifetime costs of lung transplantation: estimation of incremental costs.

Despite an expanding number of centres which provide lung transplantation, information about the incremental costs of lung transplantation is scarce. From 1991 until 1995, in The Netherlands a technology assessment was performed which provided information about the incremental costs of lung transplantation. Costs in the situation with and without a transplantation programme were compared from a lifetime perspective. Because randomization was ethically inadmissible, only costs in the situation with the programme were observed. Both conventional treatment costs and costs of the transplantation programme were registered. Costs in the situation without the programme were based on the conventional treatment costs in the situation with the programme. Due to the study period of four years, long term follow-up costs were estimated. The total incremental costs per transplanted patient were estimated at Dfl 466,767 (5% discounted costs). The main part of these costs was caused by the high costs during the lifetime follow-up of the patients.

The need for lung transplantation in The Netherlands.

The aim of this study was to assess the future need for lung transplantation in the Netherlands in the absence of limiting factors, such as a shortage of donor organs. The need was estimated using two different methods. In method 1, estimation of the need was based on data from the Dutch lung transplantation program, collected during a 4-year period (1 April 1992 until 31 March 1996). In method 2, the need was estimated using national mortality data over a 5-year period (1987-1991) preceding the start of the Dutch lung transplantation program. The results of both methods were corrected for known factors of distortion. The number of lung transplantations needed in the Netherlands in the future was estimated to range from 50 to 80 a year, which corresponds to 3.2-5.2 transplantations per million inhabitants per year. Considering the current supply of donor lungs in the Netherlands, only about one-third of the patients in need of a lung transplant in the future will be able to receive one.

[Shortage of lung donors: 3-year experience in the Groningen Academic Hospital]. / Longdonorschaarste: drie jaar ervaring in het Academisch Ziekenhuis Groningen.

OBJECTIVE: To analyse the background of the shortage of donor lungs; to present the procedure of allocation of donor lungs in the Eurotransplant region and the selection of donor lungs in the lung transplantation programme Groningen. DESIGN: Descriptive. SETTING: Groningen University Hospital. METHODS: From March 23, 1991 to December 31, 1993, the lungs of 279 multi-organ donors were offered to the lung transplantation programme of Groningen University Hospital. The assessment and selection criteria are presented. RESULTS: Only 35 out of all donor lungs offered could be used for transplantation: 24 double and 11 single lung transplants. Medical contraindications (notably pulmonary injury and hypoxaemia) were present in 155 out of the 244 (64%) lung donors. Forty-five out of 244 (18%) lung donors were rejected for logistic reasons, predominantly too little time between offer and imposed start of the explantation or long travel time. CONCLUSION: Lung donor shortage is the main factor limiting the expansion of lung transplantation programmes. Increase of the number of suitable donors can be achieved by improving donor recognition and donor management, and by improving preservation techniques allowing increased acceptable cold ischaemia periods.

[Patients in the Groningen lung transplantation program, 1990-1993; preliminary results of the medical technology assessment]. / Patiënten in het Groningse longtransplantatieprogramma, 1990-1993; voorlopige resultaten van de 'medical technology assessment'.

OBJECTIVE: Medical technology assessment of lung transplant programme in Groningen, the Netherlands. DESIGN: Descriptive evaluation study. SETTING: University Hospital Groningen. METHOD: Description of the patient route through the treatment process of the transplantation programme. RESULTS: From mid-1990 to 1-1-1994, 257 patients (M/F ratio approximately 1, median age 43 years) were evaluated. The most frequent diagnoses were: COPD/emphysema, cystic fibrosis, pulmonary hypertension and lung fibrosis. In 1991 relatively more patients came from the northern provinces, but in 1993 there was no difference from the rest of the Netherlands. Until 1-1-1994, 116 patients were excluded from the programme: 58 patients were denied transplantation in the early phase of the programme, 47 died, 6 withdrew and 5 were lost in follow-up. Until 1-1-94, 77 patients were placed on a waiting list and 35 of these underwent unilateral (n = 12) or bilateral transplantation (n = 23). One patient had a retransplantation. The 1-year survival rate was 84%. The mean time between admission and transplantation was 15 months. CONCLUSION: The results of the lung transplantation programme in Groningen are promising.

[Agreement between specialists' care and family practitioner's intention in patient referral]. / Overeenstemming van specialistische zorg en bedoeling van de huisarts bij verwijzing van patiënten.

The interaction between the general practitioner (GP) and the medical specialist during the referral process was studied in 309 referrals by GPs to medical specialists in eight hospitals in the north of the Netherlands, notably the extent of agreement between the specialist care and the intention of the GP. Furthermore the influence of two factors on the referral process was investigated: 'the clarity of the question in the referral letter' and 'the view of each other's professional tasks'. In most of the cases the GPs allowed the specialists a free hand. In the few cases the GP wanted a restricted consultation the specialist did more than the GP wanted him to do. In one of five referrals the GP or the specialist thought that the specialist had not done what the GP had asked. In most of these cases this impression was not confirmed by the objective evaluation by independent doctors. According to these the referral question was ambiguous. The GP's would like to have more influence on specialist care than the specialists were prepared to allow. The two factors each had an influence on several moments in the referral process. The main conclusion of the study is: the behaviour of the GP does not fit his attitude.

Clinical algorithms teach pediatric decisionmaking more effectively than prose.

Despite the rapidly increasing volume of medical literature, little attention has been paid to the appropriate printed format for teaching clinical content. This study attempted to determine whether a clinical algorithm (CA) or prose is more effective for teaching clinical decisionmaking. Clerkship students, preclerkship students, and pediatric house officers in five medical centers in the USA and Israel were presented with clinical algorithms and prose describing management of fever in a child under 2 years of age, and management of meningitis in children. Knowledge of decisionmaking was measured before and after learning, using audio-taped clinical problems and learning time as measured. It was concluded that CAs are more effective and more efficient than prose for teaching clinical decisionmaking. When writing about clinical decisionmaking, the use of CAs should always be considered, especially if a series of interdependent decisions is being described.

Does developmental content influence the effectiveness of anticipatory guidance?

We conducted a prospective, controlled study to evaluate the value of discussing developmental stages with mothers while providing anticipatory guidance during health maintenance visits. Eighty-three inner city mothers and their healthy, first-born infants were recruited within three days of birth and randomly assigned to either a control or intervention group. All mother-infant pairs were seen by the same pediatric provider for health maintenance visits when the infants were 2 weeks, 2 months, 4 months, and 6 months of age. At each visit, anticipatory guidance for all mothers included discussions of such age-appropriate issues as nutrition, safety, sleep, and common problematic behaviors. For the 39 intervention group mothers, the basis for such information was explained through age-specific discussions of affective, cognitive, and physical development. Dependent variables measured after the 6-month visit included maternal-infant interaction; maternal perceptions of infant temperament, family adaptation and adjustment, and satisfaction with the infant's behavior and development; and maternal satisfaction with pediatric services. Analyses of variance demonstrated no significant effect of treatment group on any of the outcome measures. These results do not support the importance of routinely discussing developmental stages during anticipatory guidance and suggest that specific, age-appropriate issues may be discussed without emphasizing the developmental basis for such information.