Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial.

BACKGROUND: Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). OBJECTIVES: To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. METHODS: This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. RESULTS: In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49). CONCLUSIONS: Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.

[«KCE Trials¼ : innovation based on practice oriented clinical trials]. / «KCE Trials¼ : des essais cliniques plus proches de la pratique.

Many questions in healthcare can only be answered after the conduct of clinical trials. For medicinal products and medical devices the industry finances most studies to bring their products to market. However, there is a need for further research in certain areas e.g. children, older people and comparative research of different treatment options (comparative effectiveness). In addition, interventions that are less industry-driven such as surgery, radiotherapy, psychotherapy, diet, physical medicine, needappropriately funded large scale clinical trials. Such clinical trials can be a good investment for the government and the healthcare payer. At the end of 2015 the Belgian Healthcare Knowledge Centre (KCE) received the mission and budget to run a programme of practice-oriented comparative clinical trials. Two years later the recruitment of patients in the first trials is ongoing. In addition to its yearly national calls for trial proposals, early in 2018 KCE launched its first international common call for comparative clinical trials with its Dutch counterpart ZonMw (BeNeFIT).

Les études cliniques financées par l'industrie, essentiellement effectuées dans le but d'obtenir la mise sur le marché de médicaments et de dispositifs médicaux, laissent de nombreuses questions cliniques sans réponse satisfaisante. Ainsi, par exemple, les produits y sont généralement comparés à un placebo, alors que la question réellement pertinente pour le clinicien serait une comparaison avec d'autres options thérapeutiques. De même, les domaines qui présentent un intérêt moindre pour l'industrie sont rarement explorés par des études à large échelle; c'est le cas, notamment, de la chirurgie, de la radiothérapie, des psychothérapies, de l'alimentation et de la médecine physique. Un programme d'études cliniques non commerciales, financé par les pouvoirs publics, permet de remédier à ces problèmes tout en constituant un excellent investissement pour les autorités de santé et le contribuable. Fin 2015, le Centre fédéral d'Expertise des Soins de Santé (KCE) a été chargé de mettre sur pied un tel programme d'études cliniques comparatives et axées sur la pratique. Deux ans plus tard, le recrutement des premiers essais bat son plein. Un appel annuel à sujets d'études a été mis en place et, début 2018, un premier appel international conjoint du KCE et de son homologue néerlandais le ZonMw a également été lancé (BeNeFIT).

[Introduction of innovative high-risk medical devices in Europe: are clinical efficacy and safety guaranteed?]. / Mise sur le marché européen des dispositifs médicaux innovants à haut risque: l'efficacité clinique et la sécurité sont-elles garanties?

BACKGROUND: Innovative high-risk medical devices, such as new types of heart valves or hip prostheses, become available on the European market more rapidly than in USA. This is due to the European legislation allowing early marketing of innovative high-risk medical devices before high-quality clinical evidence is obtained from randomized controlled trials. METHODS: We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the USA. We also discussed patient safety and the transparency of information. The literature and regulatory documents were checked. Representatives from industry, competent authorities, notified bodies, ethics committees, and health technology assessment agencies were consulted. RESULTS: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. For the patient, this implies earlier access to innovative technology, but at the risk of potential safety issues. At this moment, European requirements for clinical studies are lower for medical devices than for drugs, and data from premarket clinical trials are scarce or remain unpublished. The European Medical Device Directives are currently being reworked. CONCLUSIONS: For innovative high-risk devices, and while awaiting a reworked Medical Device Directive, patient risk should be minimized by limiting the market introduction of novel high-risk devices with minimal clinical data to physicians with the necessary training and expertise. The new European legislation should require the premarket demonstration of clinical efficacy and safety, using a randomized controlled trial if possible, and a transparent clinical review, preferably centralized.

Hospital-acquired infections in Belgian acute-care hospitals: an estimation of their global impact on mortality, length of stay and healthcare costs.

Assessing the overall burden of disease which can be attributed to hospital-acquired infections (HAIs) remains a challenge. A matched cohort study was performed to estimate excess mortality, length of stay and costs attributable to HAIs in Belgian acute-care hospitals, using six matching factors (hospital, diagnosis-related group, age, ward, Charlson score, estimated length of stay prior to infection). Information was combined from different sources on the epidemiology and burden of HAIs to estimate the impact at national level. The total number of patients affected by a HAI each year was 125 000 (per 10·9 million inhabitants). The excess mortality was 2·8% and excess length of stay was 7·3 days, corresponding to a public healthcare cost of €290 million. A large burden was observed outside the intensive-care unit setting (87% of patients infected and extra costs, 73% of excess deaths).

Hospital-acquired, laboratory-confirmed bloodstream infections: linking national surveillance data to clinical and financial hospital data to estimate increased length of stay and healthcare costs.

This matched cohort study estimates the effect of hospital-acquired bloodstream infection (HA-BSI) on length of stay (LOS) and costs during hospitalisation of 1839 patients (age range <1 to >80 years) gathered from 19 acute hospitals in Belgium. A second objective was to evaluate the impact of the choice of matching criteria. Data from national surveillance of HA-BSI were linked to hospital administrative discharge data, with respect for the patients' right to confidentiality of their health record. Controls were identified based on a set of matching factors: hospital, All-Patient Refined Diagnosis Related Groups, age, principal diagnosis, Charlson Comorbidity Index and time to infection. The results showed that, depending on the choice of matching factors, the estimation of additional LOS decreased from 26 to 10 days, with the most critical factor being the time to infection. The additional LOS attributable to HA-BSI was 9.9 days [95% confidence interval (CI): 7.8, 11.9]. The additional cost per infection was euro4900 [95% CI: euro4035, euro5750]; 58% of those costs were due to LOS, 10% were due to antibiotics, 10% due to other pharmaceutical products and 15% were due to billed medical acts. The main conclusion is that laboratory-confirmed HA-BSIs increase the LOS by 10 days for patients surviving the infection, and that the time to infection plays a crucial role in this estimation.

The 2007 Belgian national prevalence survey for hospital-acquired infections.

Despite ongoing targeted surveillance efforts, no overall in-hospital prevalence data for hospital-acquired infections (HAIs) have been published for Belgium. Sixty-three Belgian acute hospitals participated in a point-prevalence study among either all patients admitted in their institution or 50% of the patients in each ward. HAIs were registered bed-site at a single day per ward during the period October-November 2007. The diagnosis was made according to the Centers for Disease Control and Prevention (CDC) criteria implemented in a custom-made rule-based software expert system available on a portable computer. The total number of patients surveyed nationally was 17 343, from 543 distinct hospital wards. The overall prevalence of HAIs was 7.1% (95% confidence interval: 6.7-7.4%); 6.2% (5.9-6.5%) of the patients suffered from at least one HAI. Prevalence of HAIs on adult intensive care was 31.3%. The major proportion of HAIs was observed among patients admitted on non-intensive care unit (non-ICU) wards, mainly on the wards of internal medicine, surgery, geriatrics and rehabilitation. Urinary tract infections were the most common type of HAI at geriatric and rehabilitation wards. This study demonstrates that the use of a portable computer system with a designated expert system for diagnosing HAIs according to the CDC criteria in a large point prevalence study is feasible and may reduce the within-subject variation. In Belgium, the prevalence of HAIs in acute hospitals thus identified is similar to that of neighbouring countries. As more than 80% of all HAIs occur on non-ICU wards, preventive efforts need to extend beyond the ICU.

A prospective multicenter study of the efficacy and tolerability of cryopreserved allogenic human keratinocytes to treat venous leg ulcers.

Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor sites, and chronic skin ulcers with some success. Cryopreservation of these cultures allows for the production of large standardized batches that are readily available for use. The aim of the study presented in this report was to study effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on chronic lower extremity wounds. Parameters were measured to study efficacy, tolerability, pain associated with chronic wounds, and quality of life of patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had complete wound closure within 24 weeks (1 week). The time required for complete wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients attained a pain score of 0 after 12 weeks and remained stable at this score until the end of the study. Overall, the patient quality of life was better at week 24, compared to baseline values. The treatment was well tolerated, and wound infection was the most frequently occurring adverse event.

Clinical optimization and multicenter validation of antigen-specific cut-off values on the INNO-LIA ANA update for the detection of autoantibodies in connective tissue disorders.

OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line immunoassay for detection of autoantibodies to several different antigens associated with connective tissue disorders. We sought to optimize and validate the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A, RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and histones. Our aim was to achieve 98% specificity for each of the markers, with respect to differential disease controls, while maintaining sensitivity. METHODS: For optimization, the cut-off value of the different antigen lines was fixed to achieve this specificity using an in-house set of 955 patient samples. Specificity was validated at multiple sites using a different set of 330 samples obtained from 158 apparently healthy blood donors, 100 patients with a variety of infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease, and primary antiphospholipid syndrome, and 12 with psoriatic arthritis. Sensitivity was evaluated, using this optimized cut-off control, in 147 patients with scleroderma, 93 with Sjögren's disease, 40 with systemic lupus erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA ANA Update were determined using the clinical diagnosis as reference. RESULTS: The optimized cut-off values resulted in a specificity 98% or more for all LIA markers except one (histones 97.8%) in the validation set of 330 samples. The sensitivity for each marker tested in 378 samples from the target patient groups was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA Update shows uniformly high specificities combined with sensitivities very similar to those of reference assays, in a single test format.

Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus.

OBJECTIVES: To study associations between antinuclear antibodies (ANA) and signs/symptoms in patients with systemic lupus erythematosus (SLE). METHODS: A consecutive cohort of 289 patients with SLE was included; 235 fulfilled ACR criteria for SLE and were further analysed. ANA profiles were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. An extensive list of signs/symptoms was evaluated. RESULTS: Five clusters of antibodies were defined by cluster analysis: 1-antibodies to SmB, SmD, RNP-A, RNP-C, and RNP-70k; 2-antibodies to Ro52, Ro60, and SSB; 3, 4, and 5-antibodies to ribosomal P, histones and dsDNA, respectively. Significant associations (p< or =0.01) were found between anti-RNP-70k, anti-RNP-A, anti-RNP-C and Raynaud's phenomenon, between anti-RNP-A, anti-RNP-70k and leucopenia, and between anti-RNP-A, anti-RNP-C and a lower prevalence of urine cellular casts. Anti-SSA, anti-SSB were associated with xerostomia, and anti-SSB with pericarditis. Antibodies to ribosomal P were associated with haemolytic anaemia, leucopenia, and alopecia. Patients with anti-dsDNA antibodies had a higher risk for cellular casts and a lower risk for photosensitivity. Antihistone antibodies were associated with arthritis. CONCLUSIONS: In a large and consecutive cohort of patients with SLE, clusters of antibodies were identified. Previously reported associations of antibodies with symptoms were confirmed and new associations found.

Cerebrospinal fluid tau and beta-amyloid(1-42) in dementia disorders.

The reliability of cerebrospinal fluid (CSF)-tau and CSF-beta-amyloid assays for diagnosis of Alzheimer's disease and other dementing disorders such as frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) is reviewed. CSF assessment of the two proteins is useful in early diagnosis of AD and to differentiate it from FTD and DLB. Extremely high CSF-tau levels can discriminate CJD from AD.

CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Phospho-Tau International Study Group.

Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.

Serological confirmation of Chagas' disease by a recombinant and peptide antigen line immunoassay: INNO-LIA chagas.

Although screening for Trypanosoma cruzi antibodies is mandatory in most South American countries, current tests are insensitive and have poor specificity. A recently optimized line immunoassay (the INNO-LIA Chagas assay) for the serological confirmation of Chagas' disease was evaluated at a large blood bank in São Paulo, Brazil. Sera from blood donors who reacted in at least one of three serological screening assays (n = 1,604) and who returned for a follow-up were retested, and the donors were interviewed to assess their epidemiological risk. The results obtained by the confirmatory assay evaluated in this study were compared to those obtained by the three different screening assays. Upon consideration of the consensus results obtained by the three different screening assays as a "gold standard," the INNO-LIA Chagas assay showed a sensitivity of 99.4% (95% confidence interval [CI], 98.3 to 99.9) and a specificity of 98.1% (95% CI, 96.6 to 99.0) for positive (n = 503) and negative (n = 577) sera. The INNO-LIA Chagas assay confirmed the results for significantly larger numbers of positive samples of at-risk individuals independent of the number of positive screening tests (P = 0.017, Mantel-Haenszel test). In conclusion, the INNO-LIA Chagas assay reliably confirmed the presence of antibodies to T. cruzi and can be implemented as a confirmatory assay for Chagas' disease serology.

Validation of the INNO-LIA syphilis kit as a confirmatory assay for Treponema pallidum antibodies.

The commercially available diagnostic tests for syphilis are mostly based on the use of extracted antigens of Treponema pallidum. Pronounced cross-reactivities with other spirochete antigens are often reported. The aim of this study was to validate a novel multiparametric assay (the assay performed with the kit) INNO-LIA Syphilis for the confirmation of syphilis antibodies in a set of 840 documented human serum samples. All serum samples were previously tested at the French World Health Organization reference center for venereal diseases (Institute Alfred Fournier, Paris, France), with a consensus result provided for each sample. The study was conducted in two phases, with each phase involving a validation set (500 well-documented serum samples) and an exploratory set (340 serum samples) of serum samples, respectively. By measuring the sensitivity and specificity, we compared the result of the new assay with the consensus result on the basis of the results of a variable number of classical serological methods and clinical information when available. A sensitivity of 99.6% (95% confidence internal [CI], 98.5 to 99.9%) and a specificity of 99.5% (95% CI, 98.1 to 99.9%) were found for the new line immunoassay. Six of seven samples with indeterminate results by classical serology tested positive with the INNO-LIA Syphilis kit. This single multiparametric assay provides reliable confirmatory diagnostic information that must currently be obtained by the performance and interpretation of results of a combination of serological assays.

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies.

Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. A sandwich-type ELISA (INNOTEST hTAU-Ag) was used for measuring CSF-tau. Sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic CNS invasion, already showed high CSF-tau levels at baseline (>300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1,500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2,000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS+ AML. The clinical implications of both observations will be the subject of further study.

A recombinant peptide antigen line immunoassay optimized for the confirmation of Chagas' disease.

BACKGROUND: The transfusion of contaminated blood has become the major route of transmission for Chagas' disease in Brazil. Current screening tests are insensitive and yield conflicting results, while confirmatory assays do not exist. A line immunoassay (INNO-LIA Chagas Ab [INNO-LIA]) combining relevant, immunodominant recombinant and synthetic antigens on a single nylon membrane strip was evaluated for the serologic confirmation of Chagas' disease. STUDY DESIGN AND METHODS: Sera from 1062 patients and healthy residents of four Brazilian regions endemic for Chagas' disease were used for test optimization. The established confirmation algorithm was evaluated with an independent set of positive (n = 75) and negative (n = 148) samples. RESULTS: In the optimization phase, without an established comparative gold standard, the results with the INNO-LIA were compared with those obtained in four other screening assays. In the validation phase, the INNO-LIA showed a sensitivity of 100 percent (95% CI, 95.21-100) and a specificity of 99.32 percent (95% CI, 96.29-99.98) for well-characterized sera. Moreover, its specificity reached 100 percent with a set of 40 sera obtained from patients with documented leishmaniasis. The interpretation criteria defined in this study indicated that the INNO-LIA accurately detected the presence of antibodies to various specific antigens of Trypanosoma cruzi. CONCLUSION: The INNO-LIA Chagas Ab assay may become the first commercial assay to reliably confirm the presence of antibodies to T. cruzi.

Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF.

OBJECTIVE: To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. RESULTS: Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. CONCLUSIONS: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.

Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy.

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).

Tropisetron for treating established postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled study.

UNLABELLED: Tropisetron can prevent postoperative nausea and vomiting (PONV) at doses smaller than those used to control chemotherapy-induced nausea and vomiting. In this placebo-controlled study, the efficacy and tolerability of three different doses of tropisetron were compared for the treatment of established PONV after surgical procedures in general anesthesia. Of 1513 patients who satisfied inclusion criteria, 314 experiencing PONV during the first 2 h after recovery from anesthesia were treated with one of three different doses of tropisetron (0.5, 2, or 5 mg) or placebo, administered i.v. as a single dose. Patients were then observed during 24 h for efficacy and tolerability. All three doses of tropisetron were significantly better than placebo in controlling emetic episodes and in reducing the need for rescue treatment. There were no significant differences among the three doses. However, in the subgroup of patients who had previous PONV, and in those randomized for nausea alone, the 2-mg and 5-mg doses controlled emetic episodes better than the 0.5-mg dose. All studied doses of tropisetron were well tolerated and did not affect vital signs. We conclude that a single i.v. administration of tropiestron significantly reduces the recurrence of emetic episodes in patients with established PONV after elective surgery with general anesthesia. Its optimal dose seems to be 2 mg. IMPLICATIONS: Three hundred-fourteen patients suffering from postoperative nausea and vomiting received different i.v. doses of a new antiemetic drug, tropisetron, to determine the lowest effective dose. We found that a single i.v. administration of tropisetron significantly reduced postoperative nausea and vomiting after elective surgery with general anesthesia.