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.

Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis.

Although several randomized controlled trials (RCTs) have shown the efficacy of antifibrinolytic drugs in liver transplantation, their use remains debated due to concern for thromboembolic complications. None of the reported RCTs has shown a higher incidence of these complications in treated patients; however, none of the individual studies has been large enough to elucidate this issue completely. We therefore performed a systematic review and meta-analysis of efficacy and safety endpoints in all published controlled clinical trials on the use of antifibrinolytic drugs in liver transplantation. Studies were included if antifibrinolytic drugs (epsilon-aminocaproic acid, tranexamic acid (TA) or aprotinin) were compared with each other or with controls/placebo. Intraoperative red blood cell and fresh frozen plasma requirements, the perioperative incidence of hepatic artery thrombosis, venous thromboembolic events and mortality were analyzed. We identified 23 studies with a total of 1407 patients which met the inclusion criteria. Aprotinin and TA both reduced transfusion requirements compared with controls. No increased risk for hepatic artery thrombosis, venous thromboembolic events or perioperative mortality was observed for any of the investigated drugs. This systematic review and meta-analysis does not provide evidence for an increased risk of thromboembolic events associated with antifibrinolytic drugs in liver transplantation.

Cost-effectiveness of lung transplantation in relation to type of end-stage pulmonary disease.

The purpose of this study was to explore the relationship between diagnosis and the cost-effectiveness and cost-utility of lung transplantation. A microsimulation model was used, based on empirical data from the Dutch lung transplantation program, collected between 1991 and 1999. We assessed life-years, quality-adjusted life-years, and costs with and without transplantation for the diagnostic categories alfa-1 antitrypsin deficiency, COPD/emphysema, bronchiectasis, primary and secondary pulmonary hypertension, cystic fibrosis, and pulmonary fibrosis. Alfa-1 antitrypsin deficiency and bronchiectasis had the highest survival gain. Secondary pulmonary hypertension and pulmonary fibrosis had the lowest survival gain and the lowest gain of quality-adjusted life-years. As compared with COPD/emphysema, alfa-1 antitrypsin deficiency, bronchiectasis, and CF had 25%, 40% and 19% more favorable cost-effectiveness ratios, respectively. Cost-utility ratios varied less, with values of -7%, -14% and -11% for alfa-1 antitrypsin deficiency, bronchiectasis, and primary pulmonary hypertension, respectively, compared with COPD. In conclusion, our model suggests that there is considerable variation in cost-effectiveness and, to a lesser degree, in cost-utility between the different diagnostic categories. These variations are the result of differences in survival and in quality of life with and without lung transplantation.

Cost-effectiveness of the HIT programme in patients with schizophrenia and persistent auditory hallucinations.

OBJECTIVE: To examine the cost-effectiveness of Hallucination focused Integrative Treatment (HIT) in patients with schizophrenia and a history of persistent auditory hallucinations. METHOD: Costs, in and outside the health care sector, and outcomes were registered prospectively during a period of 18 months for patients who received the HIT programme and for patients in the care as usual (CAU) condition. The Positive and Negative Syndrome Scale (PANSS) was used as main outcome measure in the cost-effectiveness analysis. Bootstrap analyses provided additional information on the skewly distributed costs. RESULTS: Mean costs per patient in the HIT group (18,237 dollars) were lower than the mean costs per patient in the CAU group (21,436 dollars). Results of the PANSS were slightly in favour of the HIT group. CONCLUSION: There appears to be no significant cost-effectiveness advantage of the HIT programme over CAU. Additional analyses indicated that future application of the HIT programme will, in most cases, lead to a reduction of (non) medical costs.

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.

Thoracolumbar spinal fractures: segmental range of motion after dorsal spondylodesis in 82 patients: a prospective study.

In order to study the effect of dorsal spondylodesis on intervertebral movement in patients treated for thoracolumbar fractures, we measured the sagittal range of motion (ROM) in the segments above and below the fractured vertebral body 2 years after operation. Between 1991 and 1996, 82 consecutive patients with a fracture of the thoracolumbar spine (T12, L1, L2 and L3) were treated operatively with open reduction and stabilisation using an internal fixator, combined with transpedicular cancellous bone graft and dorsal spondylodesis. Eighteen T12, 42 L1, 17 L2 and 5 L3 fractures were included. The range of motion of two segments above and two segments below fracture level was measured. This was done on plain flexion and extension radiographs. The data were compared to normal values and to the zero distribution with the Kolmogorov-Smimov test. At all fracture levels the ROM of the segment adjacent to the disturbed endplate of the fractured body was zero (K-S test). All other evaluated segments showed significant loss of ROM (P<0.05) compared to normal values, except segment L1-L2 in L3 fractures (P=0.058). Dorsal spondylodesis at the level of the disturbed endplate in thoracolumbar spinal fractures leads to immobility in this segment, measured on flexion-extension radiographs 2 years after primary operative treatment. More than 50% loss of motion in the two adjacent levels is equivalent to complete loss of ROM in a second segment.

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.

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.

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.

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 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.

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.

Early vascular complications after pediatric liver transplantation.

Vascular complications have a detrimental effect on the outcome after liver transplantation. Most studies focus exclusively on hepatic artery thrombosis (HAT). The current study analyzed the incidence, consequences, and risk factors for HAT, portal vein thrombosis (PVT), and venous outflow tract obstruction (VOTO) in a consecutive series of 157 pediatric liver transplantations. The overall incidence of vascular complications was 21%. The incidences of HAT, PVT, and VOTO were 10%, 4%, and 6%, respectively. Patient survival after PVT and VOTO and graft survival after HAT and PVT were less compared with survival of grafts without vascular complications. To identify risk factors for vascular complications, factors related to recipient, donor, and surgical techniques were analyzed. A low donor-recipient (D/R) age ratio, long surgical time, and use of the proper hepatic artery of the recipient for arterial reconstruction were risk factors for HAT. Young age, low weight, segmental grafts, and piggyback technique were risk factors for PVT. Fulminant hepatic failure, high D/R age and weight ratios, and use of segmental grafts were related to VOTO. Vascular complications, which occurred in 21% of the pediatric liver transplantations, had a significant impact on patient and graft survival. Size disparity between donor and recipient was an important risk factor for vascular complications, especially in the case of transplantation of segmental grafts. Patient and graft survival might improve by avoiding the identified risk factors.

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.

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.

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.

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.