Economic consequences of alternative medication strategies in first episode non-affective psychosis.

BACKGROUND: Maintenance treatment appears to be successful in preventing relapses in first episode psychosis, but is also associated with side effects. Guided discontinuation strategy is a less intrusive intervention, but may lead to more relapses. In the current economic evaluation, costs and health outcomes of discontinuation strategy will be compared with the results of maintenance treatment in patients with remitted first episode psychosis. METHOD: The study was designed as a randomised clinical trial. In total 128 patients were prospectively followed for 18 months after six months of stable remission. The economic evaluation was conducted from a societal perspective. Quality-adjusted life years (QALYs) were used as primary health outcome in the economic evaluation. Relapse rates were assessed in addition to various other secondary outcomes. RESULTS: There were no relevant differences in mean costs between groups during the study. Total costs were largely influenced by costs related to admissions to psychiatric hospitals. No differences between groups were found for QALY results. CONCLUSIONS: There were no indications that either of the examined interventions is superior to the other in terms of costs or QALY results. Additional results indicated that the relapse rate in discontinuation strategy was twice as high, but without an increase in hospital admissions or negative consequences on other clinical outcomes. For a minority of remitted first episode patients, guided discontinuation strategy may offer a feasible alternative to maintenance treatment.

Predictive factors for portal fibrosis in pediatric liver transplant recipients.

BACKGROUND: Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities, to assess the clinical significance, and to identify predictive factors for these pathological changes. METHODS: The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors for the histological abnormalities in the biopsies was performed by a multivariate logistic regression analysis. RESULTS: The incidence of portal fibrosis (PF) was 31%. Liver function tests showed except for the albumin level, an increase in the PF group compared with the group without PF. Mean values of alkaline phosphatase and direct bilirubin were 264 U/liter and 3 micromol/liter, respectively, in the normal group, and 435 U/liter and 23 micromol/liter, respectively, in the PF group (P=0.043 and 0.037). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time, preservation solution, type of allograft, cytomegalovirus recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for cold ischemia time, biliary complications, and cytomegalovirus status. Acute rejection showed a negative correlation. CONCLUSIONS: The incidence of PF within 1 year post liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged cold ischemia time, biliary complications, and a positive cytomegalovirus recipient status. Acute rejection seemed to prevent for PF.

Prognostic factors for long-term actual patient survival after orthotopic liver transplantation in children.

BACKGROUND: Orthotopic liver transplantation has become the treatment of choice for children with end-stage liver disease. Although results have improved the last decades, still a considerable number of children die after transplantation. The aim of this study was to analyze long-term actual survival and to identify prognostic factors for such survival rates. METHODS: A consecutive series of 66 children receiving transplants who had or could have had a follow-up of at least 5 years was retrospectively analyzed. Actual survival and prognostic factors in relation to patient, donor, and operation related variables were assessed after multivariate analysis. RESULTS: Actual 1-, 3-, and 5-year patient survival was 86%, 79%, and 73%, respectively. A high Child-Pugh (C-P) score or C-P class C, high donor age, high blood loss index, and retransplantation were predictive factors for actual patient survival. A high blood loss index was correlated with biliary atresia, low recipient age and weight, and with previous upper abdominal operations. The duration of stay of the donor at the intensive care unit (ICU) was a predictive factor for retransplantation. CONCLUSIONS: Children with diseases eligible for liver transplantation should be seen early in the course of their disease in a transplantation center. All possible measures should be taken during the transplantation procedure to keep the blood loss at a minimum. Children with biliary atresia deserve special attention in this respect. The choice of donors has implications for survival.

Analysis of survival and morbidity after pediatric liver transplantation with full-size and technical-variant grafts.

BACKGROUND: To alleviate the shortage of size-matched whole-donor organs, too-large-for-size cadaveric donor grafts are modified by liver resection techniques. These modifications result in technical-variant liver transplantation (TVLTx). Patient and graft survival rates after TVLTx are considered comparable to those after full-size liver transplantation (FSLTx). However, morbidity after TVLTx is often underexposed. The aim of this study was to analyze the results of FSLTx and TVLTx in terms of patient and graft survival rates and morbidity. METHODS: A consecutive series of 97 primary and elective pediatric liver transplantations performed in a single center was retrospectively analyzed. Forty-seven children had a FSLTx and 50 a TVLTx (38 reduced-size liver grafts and 12 split-liver grafts). The overall median follow-up period was 3.5 years. RESULTS: There were no differences in patient and graft survival rates between FSLTx and TVLTx. However, after TVLTx there was a significantly higher complication rate (1.42 vs. 0.81 after FSLTx). TVLTx is more hampered by biliary complications (30% vs. 17%), expressed by a higher incidence of cholangitis and leakage of bile. These complications led to a significantly higher incidence of sepsis (44% vs. 19%) and a significantly higher intervention rate (0.40 vs. 1.28) after TVLTx. There was no difference in the incidence of retransplantations between FSLTx and TVLTx. CONCLUSIONS: Both FSLTx and TVLTx offer the same prognosis in terms of patient and graft survival rates for children after a primary and elective liver transplantation. However, TVLTx has a higher morbidity.

Retransplantation of the liver in children.

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.

Bronchiolitis obliterans syndrome and additional costs of lung transplantation.

STUDY OBJECTIVES: The influence of bronchiolitis obliterans syndrome (BOS) on costs after lung transplantation was investigated by comparing the costs of patients with and without this condition. DESIGN: Follow-up costs were prospectively investigated in a medical technology assessment of the Dutch Lung Transplant Program, in relation to the development of the BOS. First, average follow-up costs per week per patient were compared between patients who did or did not develop BOS. Second, in the BOS group, these costs were compared before and after the onset of BOS. SETTING: Dutch Lung Transplant Program, University Hospital of Groningen. RESULTS: Data on 53 patients (37 patients without BOS and 16 with BOS) who underwent transplantation between November 1990 and April 1995 were available. The average follow-up time of these 53 patients was 1.5 years. The follow-up costs amounted to an average (in Dutch guilders [Dfl]) of 1,774/wk for non-BOS patients, compared to 3,072/wk for BOS patients (+ 73%; p = 0.002; one Dfl = 50 cents US currency). This difference in costs was largely accounted for by an increase in used health-care resources, in particular hospitalization and medication. For the BOS patients, the average costs per week before and after the onset of BOS were 1,941 Dfl and 2,422 Dfl, respectively. CONCLUSION: BOS is associated with substantial extra costs. These findings reemphasize the need to focus efforts on prevention of BOS to enhance the cost-effectiveness of lung transplantation.

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.

Simulated waiting list prioritization for equitable allocation of donor lungs.

BACKGROUND: In lung transplantation (LTx), allocation of donor lungs is usually based on blood group, height and waiting time. Long waiting times favor patients with a slowly progressive end-stage lung disease and make the current allocation system the subject of discussion. In an attempt to equalize the chances for transplantation for every patient, irrespective of diagnosis, we investigated the effect of diagnosis-dependent prioritization on the waiting list, using a simulation model. METHODS: For the main disease categories on the waiting list, the relative risks of dying while on the waiting list were calculated using empirical data from the Dutch LTx program gathered over a period of 10 years. In a microsimulation model of the Dutch LTx program based on data from the actual situation, patients with diagnoses associated with a statistically significant increased risk of death while on the waiting list were prioritized by multiplying the time on the waiting list by the relative risk. RESULTS: Relative risks of death on the waiting list were increased significantly in patients with cystic fibrosis, primary pulmonary hypertension and pulmonary fibrosis. Prioritization resulted in an increased chance of transplantation for the prioritized diagnoses and a decreased chance for the non-prioritized diagnoses. The distribution of diagnoses after LTx was almost equal to the distribution of diagnoses on the waiting list. CONCLUSION: The simulated method of prioritization on the waiting list is a step forward to a more equitable allocation of donor lungs. Moreover, this method is clinically feasible, as long as the waiting list is updated frequently.

Cost effectiveness of selective decontamination of the digestive tract in liver transplant patients.

OBJECTIVE: To assess the cost effectiveness of selective decontamination of the digestive tract (SDD) in liver transplant patients. DESIGN: Randomised, placebo-controlled, double-blind trial with an integrated economic evaluation. SETTING: Two university hospitals in The Netherlands. Cost effectiveness was assessed from a societal perspective. PATIENTS AND PARTICIPANTS: 58 patients who underwent liver transplantation and received SDD (n = 29) or placebo (n = 29) pre- and postoperatively. INTERVENTIONS: SDD medication and placebo. MAIN OUTCOME MEASURES: Infection episodes, days of infection, costs of SDD and routine cultures, mean other direct medical costs per patient and additional costs of severe infection. RESULTS: Costs of SDD medicine and routine cultures were on average 3,100 US dollars ($US; 1997 values) per patient who underwent SDD. Both preoperatively and postoperatively, costs other than SDD and cultures did not significantly differ between the SDD and the placebo groups (preoperative, $US2,370 vs $US2,590; postoperative, $US25,455 vs $US24,915). Additional postoperative costs of severe infections were $US250 per day per patient. There were no significant differences in the mean number of infection episodes between groups. CONCLUSIONS: SDD leads to the additional costs of SDD medication and routine cultures, whereas no savings in other costs and no improvement in infection episodes are realised. Consequently, SDD may be considered as a nonefficient approach in patients undergoing liver transplantation. The additional costs of severe infection are considerable.

Antiviral treatment of idiopathic sudden sensorineural hearing loss: a prospective, randomized, double-blind clinical trial.

A subclinical viral labyrinthitis has been postulated in the literature to elicit Idiopathic Sudden Sensorineural Hearing Loss. An etiological role for the herpes virus family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, the therapeutic value of the antiherpetic drug aciclovir (Zovirax) on hearing recovery in 44 ISSHL patients receiving prednisolone is evaluated in a multicentre clinical trial. The study is designed prospectively, randomized, double-blind and placebo-controlled. Subjective parameters include hearing recovery, a pressure sensation on the affected ear, disequilibrium or vertigo and tinnitus. Audiometric parameters include pure tone and speech audiometry. A one-year follow up is obtained. Both the pressure sensation and disequilibrium or vertigo have a good prognosis, but tinnitus, occurring in most patients, has a poor prognosis. Hearing recovery prognosis depends on the severity of initial hearing loss, and not on vestibular involvement. No beneficial effect from combining aciclovir with prednisolone can be established in ISSHL.

Trends in sports injuries, 1982-1988: an in-depth study on four types of sport.

In this study, we analyzed the records of both inpatients and outpatients which were treated for acute sports injuries in the Trauma Department of the University of Groningen (The Netherlands) during the years 1982 to 1988. We examined whether there was a trend in sports injuries in this time period. The study comprised four types of sports, i.e., soccer, volleyball, gymnastics, and martial arts. The absolutely highest rates of injuries across the seven years were found in soccer, followed by gymnastics, volleyball, and martial arts. Injuries sustained at participating in soccer, volleyball, and gymnastics involved for the major part the lower extremities, followed by injuries of the upper extremities, whereas the reverse pattern was observed for patients who participated in martial arts. For all four types of sport, the ankle and foot were the most frequently site of injury of the lower extremities. Sprains and strains were the major types of injury. Most injuries were seen at ages between 10 and 30 years. The ratio of male to female patients within age groups did not differ significantly across the seven years. We concluded that, except for martial arts, the increased participation in sports in the last decade was not accompanied with a change in the patterns of sports injuries by the patients' age, sex, and number and nature of the injury. This consistency in results can be used to guide the development of prevention programs aimed at a reduction of injuries in specific sports.

[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.

[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.

Factors to consider when designing phase III clinical trials involving economic evaluations.

Given the recognized need to examine cost-effectiveness data in addition to clinical data when making decisions relating to choice of clinical interventions, there is a growing interest and experience in undertaking economic evaluations alongside clinical trials. It has been argued, when an economic evaluation is necessary for assessing the cost-effectiveness of a medical intervention, the integration of both the medical and clinical issues need to be included at the start of designing a clinical trial. A proposal has been made for how clinical researchers and health economists may cooperate successfully at the successive phases in designing a clinical trial. Therefore, discussion points for clinical researchers and health economists are given, and the possible methodological consequences of adding an economic evaluation to a trial are addressed.

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.

Alternative matrix seriation, traditional seriation, and multiple classification.

This study investigated the structural relationships between traditional seriation tasks derived from Piaget's publications and alternative matrix seriation on the one hand, and alternative matrix seriation and multiple classification on the other. Subjects were 464 children from two kindergartens and three primary schools, Grades 1 through 6 who completed these three types of tasks. Factor analysis revealed that the alternative matrix seriation tasks (often used in neo-Piagetian research) did not reflect the same underlying concept as the traditional seriation tasks derived from Piaget's publications. In contrast, we found that alternative matrix seriation referred to the same underlying concept as multiple classification. We concluded that the alternative matrix seriation tasks cannot serve as a replacement for the traditional seriation tasks in assessing a child's seriation capacity.

Rate control versus electrical cardioversion for atrial fibrillation: A randomised comparison of two treatment strategies concerning morbidity, mortality, quality of life and cost-benefit - the RACE study design.

BACKGROUND: Persistent atrial fibrillation (AF) does not terminate spontaneously and may cause left ventricular dysfunction and thromboembolic complications. For restoration of sinus rhythm electrical cardioversion (ECV) is most effective. However, AF frequently relapses, necessitating re-ECV and institution of potentially harmful antiarrhythmic drugs. If AF is accepted, rate control and prevention of thromboembolic complications using negative chronotropic drugs and warfarin is pursued. It is our hypothesis that rate control therapy is not inferior to ECV therapy in preventing morbidity and mortality. METHODS: RACE (RAte Control versus Electrical cardioversion for atrial fibrillation) is a randomised comparison of serial ECV therapy (repeat ECV as soon as possible after a relapse and institution of an antiarrhythmic drug: sotalol, class IC drug and amiodarone) and rate control therapy (resting heart rate <100 bpm using digitalis, calcium channel blockers and/or ß-blockers) in patients with persistent AF. Morbidity (heart failure, side effects of drugs, thromboembolic complications, bleeding and pacemaker implantation), mortality, quality of life and cost-effectiveness are primary and secondary endpoints. Included are patients with a recurrence of persistent AF, present episode <1 year and a maximum of two previous successful ECVs during the last two years. This study is a multicentre study in 31 centres throughout the Netherlands. All 520 patients have now been included. Follow-up is two years. The results are expected this year.