Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation.

BACKGROUND: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.

A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia.

BACKGROUND: An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) compared to enzymatic testing and standard weight-based dosing. PROCEDURE: A cost-effectiveness analysis was conducted from a health care system perspective comparing costs and consequences over 3 months. Decision analysis was used to evaluate the impact of TPMT tests on preventing myelosuppression and improving survival in ALL patients receiving 6-MP. Direct medical costs included laboratory tests, medications, physician services, pharmacy and inpatient care. Probabilities were derived from published evidence. Survival was measured in life-months. The robustness of the results to variable uncertainty was tested in one-way sensitivity analyses. Probabilistic sensitivity analysis examined the impact of parameter uncertainty and generated confidence intervals around point estimates. RESULTS: Neither of the testing interventions showed a benefit in survival compared to weight-based dosing. Both test strategies were more costly compared to weight-based dosing. Incremental costs per child (95% confidence interval) were $277 ($112, $442) and $298 ($392, $421) for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing. CONCLUSIONS: The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective.

The role of routine assays of serum amylase and lipase for the diagnosis of acute abdominal pain.

INTRODUCTION: We aimed to evaluate the role of routine measurements of serum amylase and lipase in the diagnosis of acute abdominal pain. PATIENTS AND METHODS: We identified all patients who had serum amylase and lipase assays over a 62-day period at a single university teaching hospital and reviewed their case notes. RESULTS: We excluded 58 of the 1598 patients on grounds of ineligibility (< 18 years of age and those transferred from other hospitals). A complete data set was obtained for 1520 (98.7%) of the remaining 1540 patients. Only 9.1% of requests were based on a clinical suspicion of acute pancreatitis. Of the 44 (2.9%) patients who had acute pancreatitis, only 28 (63.6%) had an associated rise in serum amylase and/or lipase 3 times above the maximum reference range, the remainder being diagnosed radiologically. At this cut-off range, the sensitivity and specificity for serum amylase were 50% and 99%, and those for serum lipase 64% and 97%, respectively. CONCLUSIONS: Routine measurements of serum amylase and lipase are unhelpful in the diagnosis of acute abdominal pain unless there is clinical suspicion of acute pancreatitis. In these patients, assay of lipase alone is preferable to assay of amylase alone or both enzymes.

TPMT testing before azathioprine therapy?

Azathioprine has been in use for decades as an immunosuppressant treatment for various autoimmune diseases. It is a prodrug of mercaptopurine, a substance that is subsequently metabolised by several alternative pathways, one of which involves the enzyme thiopurine methyltransferase (TPMT). Some people have deficiency of TPMT because of genetic mutations. This has been widely said to occur in around 3 in 1,000 individuals;1 however, studies in recent years have suggested a prevalence of up to 6 in 1,000.2,3 These people are at great risk of developing severe, potentially life-threatening bone marrow toxicity when treated with conventional doses of azathioprine or mercaptopurine. It is possible to test patients for TPMT activity before starting treatment with these drugs. Here we review the evidence about such testing, and discuss whether it should be used for patients being considered for azathioprine therapy.

Is there yet any place for reagent strips in diagnosing spontaneous bacterial peritonitis in cirrhotic patients? An accuracy and cost-effectiveness study in Brazil.

BACKGROUND: Diagnosis of spontaneous bacterial peritonitis (SBP) is currently based on ascitic cell counting, but there is a need for a more simple and rapid diagnostic tool. The objectives of this study are to evaluate the accuracy of reagent strips in diagnosing SBP and compare their costs with total and differential cell counts. PATIENTS AND METHODS: 71 cirrhotic in- and outpatients were consecutively included (159 samples). Spontaneous bacterial peritonitis was defined as neutrophil cells >or= 250/microL. The cutoff values for each reagent strip were defined by a receiver operating characteristic (ROC) curve. Sensitivity (S), Specificity (Sp), Positive and Negative Predictive Values (PPV and NPV), Accuracy (Ac) and cost-effectiveness (US$) in comparison to cell count exam were calculated. RESULTS: Spontaneous bacterial peritonitis was diagnosed in 17 patients (23.9%), 11 of them with positive culture (64.7%). The best cutoff points found in ROC curves were 1+ for Multistix 10 SG and ca. 75 for Choiceline 10 (Multistix 10 SG S = 80%, Sp = 98.5%, PPV = 90.9%, NPV = 96.2%, Ac = 95%; Choiceline 10 S = 76.9%, Sp = 97.7%, PPV = 87%, NPV = 95.6%, Ac = 94%). In terms of cost-effectiveness by cost/accuracy, cell count was 41.5, Multistix 10 SG 0.57, and Choiceline 10, 0.19 (P < 0.001). CONCLUSION: Reagent strips are a useful tool for diagnosing SBP in cirrhotic patients, but they have some limitations. Strips are especially indicated when total and differential cell counts are not quickly available or sometimes unavailable. They are also indicated as screening test in emergency rooms to anticipate the diagnosis of SBP and allow its early treatment. It's an interesting option in developing countries.

Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease.

BACKGROUND: Myelosuppression occurs in 2-7% of inflammatory bowel disease (IBD) patients treated with azathioprine, and can be associated with reduced activity of thiopurine methyltransferase (TPMT) in some patients. It has been proposed that pretreatment assessment of TPMT status reduces the incidence of toxicity and is cost-effective. AIMS: To determine if screening for TPMT status predicts side-effects to azathioprine in patients with IBD and to ascertain whether screening by TPMT enzyme activity or genotype is superior. METHODS: Sequential IBD patients were identified and azathioprine tolerance recorded. Blood was collected for measurement of TPMT activity and TPMT*3C, TPMT*3A and TPMT*2 genotypes. RESULTS: Of 130 patients, 25% stopped azathioprine because of toxicity. Four patients experienced severe myelosuppression (WCC < 2). Eleven of 17 patients with reduced TPMT activity were heterozygotes, including one patient with marked TPMT deficiency who experienced severe myelosuppression. There was no association between intermediate TPMT deficiency and any side-effect. CONCLUSIONS: Moderate reduction of TPMT activity in heterozygotes was not associated with toxicity, but very low TPMT activity caused severe myelosuppression in one patient. This would have been predicted by measuring TPMT activity but not by genotyping. Measurement of TPMT activity may therefore be superior to genotype in predicting severe myelosuppression.

[Urease test of the gastric content deposits for diagnosis of Helicobacter pylori infection in the gastric mucosa].

A rapid urease test was applied to the examination of the deposit of gastric juice for diagnosing H. pylori in the gastric mucosa. Two hundred and twenty patients blindly randomized were examined in a case control study. The standard rapid urease test kit Jatrox-H.p.-Test (Rohm Pharma, Germany) was used to determine urease activity in the deposit of gastric juice and duodenal [n = 110 (Group 1)] and gastroduodenal [n = 110 (Group 2)] mucosae. Giemsa staining was employed as a comparison method to examine H. pylori infection in the gastric and duodenal mucosae. The availability of regions of duodenal metaplasia was confirmed by periodic acid-Schiff and alcian blue (Serva) staining tests (pH 1.0 and 2.5, respectively). The results of evaluation of the efficiency of the rapid urease test of gastric juice deposit and gastric and duodenal mucosae in Groups 1 and 2 were as follows: sensitivity (SE) (0.97, 0.99, 0,96), specificity (SP) (0.97, 0.97, 0.99), prevalence (0.64, 0.67, 0.24), test accuracy (TA) (0.96, 0.98, 0.98), negative (0.95, 0.97, 0.99) and positive (0.98, 0.99, 0.96) predictive values; positive (38.8, 33.0, 96.0) and negative (0.03, 0.01, 0.04) likelihood ratios. It is expedient to employ the rapid urease test for the diagnosis of H. pylori infection in the stomach (Se 96-99%, Sp 97%, TA 97-98%). When the test of gastric juice deposit and gastric biopsy is positive, the probability of gastric H. pylori availability is 98-99%. When the test is negative (the probability of H. pylori absence is 95-97%), duodenal biopsy is made. When the test of duodenal biopsy is positive, the probability of H. pylori availability is 96%. When it is negative, the probability of H. pylori absence is 99%. An algorithm of use of the rapid urease test to diagnose H. pylori in different intestinal parts (stomach, duodenum) has been developed.

Dynamic decision analysis to determine optimal treatment duration in chronic hepatitis C.

BACKGROUND: Current guidelines for stopping treatment of chronic hepatitis C are based on hepatitis C ribonucleic acid measurements at 12 and 24 weeks. AIM: To explore an alternative approach for making individualized recommendations about treatment duration, based on simple alanine aminotransferase tests and on cost-per-cure. METHODS: We analysed individual patient data from 13 randomized, controlled trials with interferon alone or combined with ribavirin. Using multiple logistic regression, we built a model that estimated the probability of sustained virological response for treatment durations of 24 and 48 weeks. Decisions to prolong treatment were based on an increase in probability of sustained virological response. If the increase was 10%, the cost-per-cure became decisive with a limit of 50,000. RESULTS: Noncirrhotics with genotype 2 or 3 did not benefit when treatment was continued beyond 24 weeks. Sustained virological response rates in cirrhotic patients increased by 14-47% if treatment was continued up to 48 weeks. In noncirrhotic genotype 1 or 4 patients who had elevated alanine aminotransferase levels at week 4, the probability of sustained virological response increased by <10% if treatment was continued up to 48 weeks; the cost-per-cure for these patients would exceed 50,000. CONCLUSION: The dynamics of alanine aminotransferase levels and cost-per-cure provides a useful alternative to determine the duration of therapy in chronic hepatitis C.

A heterogeneous enzymatic assay for quantification of Plasmepsin II activity and the evaluation of its inhibitors.

The emergence and worldwide spreading of Plasmodium falciparum strains that shown to be resistant to traditional drugs is considered a very serious health problem, given the high mortality and morbidity rate of Malaria. In the search for new drugs against this parasite, Hb hydrolyzing enzymes, such as Plasmepsin II (Plm II), have been classified as very promising targets for therapeutic attacks. In this work, it is developed a cheap and high-throughput heterogeneous enzymatic assay for measuring Plasmepsin II activity in order to use it as a tool in the discovery of new inhibitors of this enzyme. In this assay, Plasmepsin II acts upon a solid-phase bound synthetic peptide (DU2) whose sequence comprises the cleavage site F(33)-L(34) present in Hb alpha-chain. The peptide surface density is quantified by means of a classical ELISA-based procedure. In order to estimate the kinetic constants of the system and to quantify both, enzymatic and inhibitory activity, it was used a model for the kinetics of enzyme quasi-saturable systems previously developed by our group, that fitted very well to the experimental data. It was used Pepstatin as a model inhibitor of Plasmepsin II and the resulting dose-response relation agreed with the expected behavior for the Pepstatin-Plasmepsin II pair under the employed experimental conditions.

Evaluation of a liquid urease test (LUT) for detection of Helicobacter pylori.

UNLABELLED: The aim of our study was to develop a rapid diagnostic urease test to demonstrate the presence of Helicobacter pylori in the Endoscopy room. MATERIALS AND METHODS: 200 consecutive patients referred to gastroscopy for different indications, were included in this study. One antral biopsy sample was obtained to be immersed in our test. The same sample was used for histological evaluation, considered to be the gold standard method for diagnose of Helicobacter pylori infection. RESULTS: 135 patients (67.5%) were found positives and 65 patients (32.5%) were negatives in our test. 128 patients (64%) showed Helicobacter pylori on histological examination. Our test showed a sensitivity of 91%, specificity of 88.1%, and positive and negative predictive values of 95% and 80% respectively. A remarkable correlation between density of Helicobacter pylori and reading time was also observed, where a high density of the bacteria reduced the reaction time in this liquid test. Furthermore, an overall accuracy of 90% was shown, which is comparable with other available commercial tests. CONCLUSION: LUT is easy to handle, cost effective and fast, with a high positive predictive value.

Evaluación de un test líquido de UREASA ( LUT ) para la detección de Helicobacter pylori / Evaluation of a liquid urease test ( LUT ) for detection of Helicobacter pylori

The aim of our study was to develop a rapid diagnostic urease test to demonstrate the presence of Helicobacter pylori in the Endoscopy room. MATERIALS AND METHODS: 200 consecutive patients referred to gastroscopy for different indications, were included in this study. One antral biopsy sample was obtained to be immersed in our test. The same sample was used for histological evaluation, considered to be the gold standard method for diagnose of Helicobacter pylori infection. RESULTS: 135 patients (67.5%) were found positives and 65 patients (32.5%) were negatives in our test. 128 patients (64%) showed Helicobacter pylori on histological examination. Our test showed a sensitivity of 91%, specificity of 88.1%, and positive and negative predictive values of 95% and 80% respectively. A remarkable correlation between density of Helicobacter pylori and reading time was also observed, where a high density of the bacteria reduced the reaction time in this liquid test. Furthermore, an overall accuracy of 90% was shown, which is comparable with other available commercial tests. CONCLUSION: LUT is easy to handle, cost effective and fast, with a high positive predictive value. (AU)

Isolated pleural fluid lactic dehydrogenase level: a cost effective way of characterizing pleural effusions.

BACKGROUND: Characterization of pleural effusion into an exudate or transudate is usually the first step in diagnostic evaluation. Light's criteria have been universally accepted as gold standard in this regard. We wanted to see the utility of isolated pleural fluid lactic dehydrogenase level (representing one of Light's classical criteria) in characterizing pleural effusion in our setting. We also wanted to compare the accuracy of commonly used conventional criteria with Light's criteria of isolated pleural fluid lactic dehydrogenase. METHODS: Patients who underwent diagnostic thoracentesis for one-year period were studied. Characterization of pleural effusions using biochemical criteria including pleural fluid protein, lactic dehydrogenase level (LDH), red blood cell (RBC) count and white blood cell (WBC) count were identified and compared with predetermined clinical criteria (gold standard). For each biochemical criteria sensitivity, specificity, positive predictive value and negative predictive value were calculated. RESULTS: Sixty-two patients underwent diagnostic thoracentesis. Sixteen were excluded, as they did not fulfill predetermined clinical criteria. Eight patients had transudative effusion vs. 38 exudates. LDH was found to be the most sensitive (97.2%) while WBC > 1000/mm3 was the most specific (100%) of all the criteria looked at. The overall accuracy was highest for Light's criteria of isolated LDH > 200 IU/litre (95.6%) followed by pleural fluid protein, WBC count and RBC count. CONCLUSION: We conclude that isolated pleural fluid LDH, as a representative of classical Light's criteria, is the most accurate criteria for characterizing pleural effusions. Due to its low accuracy isolated pleural fluid protein should not be ordered routinely. This approach may result into potential cost savings in our economically restraint society.

The effect of a change from conventional cardiac enzymes to troponin I on overall hospital costs in patients with suspected myocardial infarction.

A random sample of patients presenting to this hospital in 1996 and 2000 with chest pain was assessed retrospectively with respect to patient bed stay and associated costs. The laboratory testing protocol had been changed from traditional cardiac markers AST, CK and CKMB, to troponin I, in the intervening period. The average bed stay for patients with chest pain of non-AMI origin was reduced by 2 days, as a result of the change in testing protocol. As ward costs contribute 49% of total cost of treatment, this resulted in decreased cost per patient, and more efficient use of hospital beds.

Routine measurement of pleural fluid amylase is not indicated.

BACKGROUND: The routine measurement of pleural fluid amylase is frequently recommended, but the cost-effectiveness of this procedure is unknown. METHODS: To assess the utility of routine measurement of pleural fluid amylase in evaluating pleural effusions, we measured amylase, glucose, lactate dehydrogenase, and protein levels and blood cell counts in 379 patients undergoing thoracentesis during a 22-month period from 1997 to 1999. Of these, 199 had effusions after cardiac surgery; 61, malignant; 48, transudative; 28, parapneumonic; 2, chylous; 2, rheumatoid; 1, tuberculous; and 1, from chronic pleuritis. There were 37 exudates of unknown origin. RESULTS: Measurement of pleural fluid amylase levels did not assist in determining the origin of the effusion in any of the patients. Amylase levels greater than 100 U/L (normal serum level in our laboratory is 30-110 U/L) were found in 5 (1.3%) of 379 patients: 1 patient with congestive heart failure (amylase, 173 U/L), 2 with post-cardiac surgery effusions (144 U/L and 130 U/L), 1 with pneumonia (109 U/L), and 1 with lung cancer (105 U/L). CONCLUSIONS: The routine measurement of pleural fluid amylase levels is neither clinically indicated nor cost-effective. We suggest that pleural fluid serum amylase levels be measured only if there is a pretest suspicion of acute pancreatitis, chronic pancreatic disease, or esophageal rupture.

Helicobacter pylori culture from a positive, liquid-based urease test for routine clinical use: a cost-effective approach.

BACKGROUND: The aim of our study was to test the feasibility of culturing Helicobacter pylori directly from biopsies aimed for rapid urease test in routine clinical practice. MATERIALS AND METHODS: In 260 consecutive patients referred for gastroscopy because of dyspepsia one antral biopsy was routinely used for our "in house" rapid urease test (RUT). Positive biopsies were placed in a transport medium and sent to the laboratory. The biopsies were cultured and incubated at 37 degrees C for 5-7 days. H. pylori was identified and routinely tested for antimicrobial resistance by using the E-test. RESULTS: In 118 out of 260 patients (45%) the urease test turned positive and the growth of H. pylori was sufficient to allow testing of antimicrobial resistance. CONCLUSION: H. pylori could be cultured from almost all positive RUT specimens. A liquid RUT is thus more suitable for culture, saving additional biopsies.