Adverse Events and Economic Burden Among Patients Receiving Systemic Treatment for Mantle Cell Lymphoma: A Real-World Retrospective Cohort Study.

BACKGROUND/AIM: Limited published real-world data describe adverse events (AEs) among patients treated for mantle-cell lymphoma (MCL). The aim of this retrospective study was to describe treatment patterns, AEs, and associated healthcare costs. PATIENTS AND METHODS: Patients had two or more claims coded for MCL diagnosis, the first claim date (07/01/2012-05/31/2017) was the index date. Patients with pre-index MCL diagnosis or systemic treatment, or hematopoietic stem cell transplantation were excluded. Cohorts by regimen were followed for up to three lines of therapy. RESULTS: Patients (n=395; median age 72 years; 31% female) were observed over a total of 576 lines of therapy, the most common being bendamustine plus rituximab; rituximab monotherapy; R-CHOP; and ibrutinib. The most frequent AEs were hypertension (40.5%), anemia (37.7%), and infection (36.1%). However, hepatotoxicity ($19,645), stroke ($18,893), and renal failure ($9,037) were associated with the highest medical costs per patient per month. CONCLUSION: Among patients receiving common systemic treatments for MCL, AEs occurred frequently; some imposed substantial inpatient care costs.

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

Transcriptional, Functional, and Mechanistic Comparisons of Stem Cell-Derived Hepatocytes, HepaRG Cells, and Three-Dimensional Human Hepatocyte Spheroids as Predictive In Vitro Systems for Drug-Induced Liver Injury.

Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems-hepatocytes derived from induced pluripotent stem cells, HepaRG cells, and three-dimensional primary human hepatocyte (PHH) spheroids-at transcriptional and functional levels in a multicenter study to evaluate their potential as predictive models for drug-induced hepatotoxicity. Transcriptomic analyses revealed widespread gene expression differences between the three cell models, with 8148 of 17,462 analyzed genes (47%) being differentially expressed. Expression levels of genes involved in the metabolism of endogenous as well as xenobiotic compounds were significantly elevated in PHH spheroids, whereas genes involved in cell division and endocytosis were significantly upregulated in HepaRG cells and hepatocytes derived from induced pluripotent stem cells, respectively. Consequently, PHH spheroids were more sensitive to a panel of drugs with distinctly different toxicity mechanisms, an effect that was amplified by long-term exposure using repeated treatments. Importantly, toxicogenomic analyses revealed that transcriptomic changes in PHH spheroids were in compliance with cholestatic, carcinogenic, or steatogenic in vivo toxicity mechanisms at clinically relevant drug concentrations. Combined, the data reveal important phenotypic differences between the three cell systems and suggest that PHH spheroids can be used for functional investigations of drug-induced liver injury in vivo in humans.

The incidence, presentation, outcomes, risk of mortality and economic data of drug-induced liver injury from a national database in Thailand: a population-base study.

BACKGROUND: Toxic liver diseases are mainly caused by drug-induced liver injury (DILI). We assessed incidences and outcomes of DILI including associated factors for mortality. METHODS: We performed a population-based study of hospitalized patients with DILI. Information was retrieved from the Nationwide Hospital Admission Data using ICD-10 code of toxic liver diseases (K71) and additional codes (T36-T65). The associated factors were analyzed with log-rank test, univariate and multiple cox regression analysis. RESULTS: During 2009-2013, a total of 159,061 (average 21,165 per year) admissions were related to liver diseases. 6,516 admissions (1,303 per year) were due to toxic liver diseases. The most common type of toxic liver disease was acute hepatitis (33.5 %). In-hospital and 90-day mortality rates were 3.4 % and 17.2 %. DILI with cirrhosis yielded the highest in-hospital and 90-day mortality rates (15.8 % and 47.4 %). Acetaminophen, cirrhosis and age ≥ 60 years were seen in 0.5 %, 8.3 % and 50.1 % of patients who died versus 5 %, 2.3 % and 32.4 % of survivors. Factors associated with mortality were cirrhosis (HR 2.72, 95 % CI: 2.33-3.19), age ≥60 years (HR 2.16, 95 % CI: 1.96-2.38), human immunodeficiency viral infection (HR 2.11, 95 % CI: 1.88-2.36), chronic kidney disease (HR 1.59, 95 % CI: 1.33-1.90), chronic obstructive pulmonary disease and bronchiectasis (HR 1.55, 95 % CI: 1.17-2.04), malnutrition (HR 1.43, 95 % CI: 1.10-1.86) and male (HR 1.31, 95 % CI: 1.21-1.43). Acetaminophen DILI yielded lower risks of mortality (HR 0.24, 95 % CI: 0.13-0.42). The most common causes of DILI were acetaminophen (35.0 %) and anti-tuberculous drugs (34.7 %). CONCLUSIONS: DILI is an uncommon indication for hospitalization carrying lower risks of death except in patients with non-acetaminophen, cirrhosis, elderly or concomitant diseases.

Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury?

OBJECTIVES: To evaluate the failure rate of the 150-treatment line for paracetamol overdose in Hong Kong, and the impact if the treatment threshold was lowered. SETTING: Public hospitals, Hong Kong. PATIENTS: All patients with acute paracetamol overdose reported to the Hong Kong Poison Information Centre from 1 January 2011 to 31 December 2013 were studied and analysed for the timed serum paracetamol concentration and their relationship to different treatment lines. Presence of significant liver injury following paracetamol overdose was documented. The potential financial burden of different treatment lines implemented locally was estimated. RESULTS: Of 893 patients, 187 (20.9%) had serum paracetamol concentration above the 150-treatment line, 112 (12.5%) had serum paracetamol concentration between the 100- and 150-treatment lines, and 594 (66.5%) had serum paracetamol level below the 100-treatment line. Of the 25 (2.8%) patients who developed significant liver injury, two were between the 100- and 150-treatment lines, and the other two were below the 100-treatment line. The failure rate of the 150-treatment line was 0.45%. Lowering the treatment threshold to the 100-treatment line might lower the failure rate of the treatment nomogram to 0.22% but approximately 37 more patients per year would need to be treated. It would incur an additional annual cost of HK$189 131 (US$24 248), and an additional 1.83 anaphylactoid reactions per year. The number needed-to-treat to potentially reduce one significant liver injury is 112. CONCLUSIONS: Lowering the treatment threshold of paracetamol overdose may reduce the treatment-line failure rate. Nonetheless such a decision must be balanced against the excess in treatment complications and health care resources.

[Pharmacoeconomic Analysis of the Use of Hepatoprotectors in Management of Drug-Associated Liver Injury Due to Hodgkin's Lymphoma Chemotherapy].

The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use.

[Pharmacoeconomic profiles of four hepatoprotective drugs used for the treatment of drug-induced liver injury].

OBJECTIVE: To perform a pharmacoeconomic evaluation of the efficacies of therapeutic schemes involving four hepatoprotective drugs for the treatment of drug-induced liver injury (DILI). METHODS: The principle of decision tree analysis in pharmacoeconomics was applied to perform a retrospective analysis using a meta-analyses approach to evaluate the data from randomized controlled trials of four common therapeutic schemes.The key parameters for evaluating efficacy and safety of each were identified by searching the official data, relevant literature and expert opinions, and included the parameters of consumption and unit cost with respect to a variety of health resources. RESULTS: The hepatoprotective drug showing the greatest efficacy (4.5118) and safety for treating DILI was bicyclol; this drug also had a lower incremental cost-effectiveness ratio (ICER; 245.0118) than the other three therapeutic schemes.The tioproninenteric-coated tablet had the lowest cost (296.9536) among the four, but also had the worst efficacy (4.1352). Bicyclol had the lowest cost/benefit ratio (5.32) and ICER (4.93) among all the therapeutic schemes evaluated.Sensitivity analyses confirmed the robustness of these results. CONCLUSION: According to this pharmacoeconomic evaluation, the bicyclol therapeutic strategy is the most cost-effective choice for DILI.

Compensation for work-related hematologic, liver, and infectious diseases.

Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.

Compensation for Work-Related Hematologic, Liver, and Infectious Diseases

Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.

[Efficiency of initiation with ambrisentan versus bosentan in the treatment of pulmonary arterial hypertension]. / Eficiencia del inicio con ambrisentan frente a bosentan en el tratamiento de la hipertensión arterial pulmonar.

OBJECTIVE: To evaluate the efficiency of initiation with endothelin receptor antagonists, ambrisentan or bosentan, followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary arterial hypertension, from the Spanish National Health System perspective. METHODS: A Markov model was developed based on the four New York Heart Association functional classes. A panel of three experts reached a consensus on patient management based on clinical practice. Patients revised their treatment every 12 weeks, based on their health status and previous medication records. Pharmacological treatment costs and costs associated with very frequent adverse events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in qualityadjusted life years (QALY). A probabilistic sensitivity analysis was performed. RESULTS: No clinically relevant differences in QALY per-patient and year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902, respectively. Initiation with ambrisentan resulted in lower pharmacological treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In the sensitivity analysis, initiation with ambrisentan resulted in a negative significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101]. CONCLUSIONS: Initiation with ambrisentan followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at lower costs than initiation with bosentan.

Objetivo: Se pretende evaluar la eficiencia del tratamiento secuencial de combinación de la hipertensión arterial pulmonar iniciado con antagonistas del receptor de la endotelina, ambrisentan o bosentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, desde la perspectiva del Sistema Nacional de Salud. Métodos: Se desarrolló un modelo de Markov basado en las cuatro clases funcionales de la New York Heart Association. Un panel de tres expertos alcanzó un consenso sobre el manejo del paciente basado en la práctica clínica. Los pacientes revisaron su tratamiento cada 12 semanas, en función de su estado de salud y de la medicación recibida previamente. Se incluyeron costes farmacológicos y costes asociados al manejo de eventos adversos (EA) muy frecuentes, en un horizonte de 60 semanas. Los resultados se expresaron en términos de los años de vida ajustados por calidad (AVAC). Se realizó un análisis de sensibilidad probabilístico. Resultados: No se encontraron diferencias clínicamente relevantes en los AVAC por paciente y año para el inicio con ambrisentan y bosentan: 0,6853 y 0,6902, respectivamente. El inicio con ambrisentan resultó en un coste farmacológico y asociado al manejo de EA menor: 35.550 ??y 117 ??frente a 40.224 ??y 171 ?. En el análisis de sensibilidad, el inicio con ambrisentan presentó una diferencia de costes totales negativa y significativa: -4.982 ?; IC95%[-8.014 ?; -2.500 ?]; mientras que no se detectaron diferencias significativas en los AVAC: -0,0044; IC95%[-0,0189; 0,0101]. Conclusiones: El tratamiento secuencial de combinación de la HAP iniciado con ambrisentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, proporciona resultados en salud comparables y menores costes que el tratamiento iniciado con bosentan.

Paracetamol toxicity: What would be the implications of a change in UK treatment guidelines?

BACKGROUND: Treatment of single-time-point ingestion acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is guided by plotting a timed plasma paracetamol concentration on established nomograms. Guidelines in the UK differ from those in the U.S. and Australasia by having two treatment lines on the nomogram. Patients deemed to be at 'normal' risk of hepatotoxicity are treated using the treatment line starting at 200 mg/L at 4 h post-ingestion; those at higher risk are treated using the 'high risk' treatment line starting at 100 mg/L at 4 h post-ingestion. AIM: To examine the effect on treatment numbers if UK guidelines were to adopt a single treatment line nomogram or lower, risk-stratified treatment lines. METHODS: We undertook a retrospective analysis of a series of acute single-time-point paracetamol poisonings presenting to our inner city emergency department. Treatment numbers and effect on treatment costs were modelled for three alternative scenarios: a 150 line-a combined single treatment line starting at a 4 h concentration of 150 mg/L, a 100 line-a combined single treatment line starting at a 4 h concentration of 100 mg/L, and a 150/75 line-a double treatment line at the lower concentrations of 150 mg/L for normal risk and 75 mg/L for high risk patients. RESULTS: A total of 1,214 cases were identified. Under current UK guidance, 133 (11.0%) high risk cases and 98 (8.1%) normal risk cases needed treatment (total 231, 19.0%). A 150 line would result in 87 (7.2%) high risk cases and 155 (12.8%) normal risk cases needing treatment (total 242, 19.9%). A 100 line would result in 133 (11.0%) high risk and 251 (20.7%) normal risk cases needing treatment (total 384, 31.6%). A 150/75 line would result in 153 (12.6%) high risk and 155 (12.8%) normal risk cases needing treatment (total 308, 25.4%). CONCLUSIONS: Both a 100 line and a 150/75 line would result in a large increase in the number of patients being treated and an associated increase in the costs of treatment. A single 150 mg/L treatment line would simplify treatment algorithms and lead to a similar number of patients being treated with NAC overall. A potential concern however is whether any of the high risk cases that would no longer be treated might develop significant hepatotoxicity. After consideration of the evidence for dual treatment lines, we feel that these risks are small and that it is worth reconsidering a change of treatment recommendations to a single 150 line.

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka.

BACKGROUND: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. METHODS: Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. RESULTS: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes. CONCLUSIONS: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours.

[Antibiotic induced hepatotoxicity]. / Hépatotoxicité médicamenteuse due aux antibiotiques.

Drug-induced liver injury (DILI) is the most common cause of drug withdrawal of the market though it remains quite seldom. Actually, its incidence reaches about 1/100000 prescriptions. Antibiotics are the most implicated substances: 3 clinical cases are presented. The clinical manifestations are broad, appear between 5 to 90 days after the introduction of the drug and range from an asymptomatic patient to an acute hepatic failure. This diagnosis is difficult to establish. After excluding a biliary obstruction and a septic cholangitis at first, many additional investigations can be performed, but induce considerable costs. Drug history is the key element of the diagnostic approach. An algorithm is presented at the end of this article to prevent expensive, invasive and useless investigations.

Managing acute acetaminophen poisoning with oral versus intravenous N-acetylcysteine: a provider-perspective cost analysis.

BACKGROUND: Acetaminophen (APAP) overdose, which can lead to hepatotoxicity, is the most commonly reported poisoning in the United States and has the highest rate of mortality, with more than 100,000 exposures and 300 deaths reported annually (1) . The treatment of choice, N-acetylcysteine (NAC), is effective in both oral (PO) and intravenous (IV) formulations. The main difference in therapies, other than administration route, is time to complete delivery--72 hours for PO NAC versus 21 hours for IV NAC, according to full prescribing information. This distinction is the primary basis for variation in management costs for hospitalized patients receiving these products. OBJECTIVES: To quantify and compare full treatment costs from the provider perspective to manage acute APAP poisoning with either PO or IV NAC in a standard treatment regimen. METHODS: A cost model was developed and populated with published data comprising probabilities of potential clinical outcomes and the costs of resources consumed during patient care. RESULTS: For patients who present <10 hours post-ingestion, the estimated total cost of care with PO NAC in the treatment regimen is $5,817 (ICU patients) or $3,850, (ward patients) compared with $3,765 and $2,768 for similar care with IV NAC. Potential cost savings equal - $2,052 (-35%) or -$1,083 (-28%), respectively, in favor of IV NAC. Similar potential savings were estimated for patients presenting 10-24 hours post-ingestion. CONCLUSION: IV NAC is the less costly therapeutic option for APAP poisonings, based on simulation modeling and retrospective data. The current economic evaluation is restricted by the absence of comparative data from head-to-head, matched-cohort studies and the limitations common to retrospective APAP toxicology datasets. Additional research could refine these results.

[Cost of nucleoside analogue reverse transcriptase inhibitor-related toxicity in HIV-1-infected patients]. / Costes de la toxicidad asociada a los análogos de nucleósidos inhibidores de la transcriptasa inversa en pacientes con infección por el VIH-1.

OBJECTIVE: To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV-1-infected patients. METHODS: . A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians. RESULTS: The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 euro, which included 1789 euro in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 euro in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 euro), lipodystropy (535 euro) and peripheral neuropathy (533 euro). CONCLUSION: Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies.

Costes de la toxicidad asociada a los análogos de nucleósidos inhibidores de la transcriptasa inversa en pacientes con infección por el VIH-1 / Cost of nucleoside analogue reverse transcriptase inhibitor-related toxicity in HIV-1-infected patients

Objetivo. Estimar el impacto de la toxicidad asociada a los inhibidores de la transcriptasa inversa análogos de nucleósidos (ITIAN) en el coste total del tratamiento de pacientes con infección por el virus de la inmunodeficiencia humana tipo 1 (VIH-1). Métodos. Se ha diseñado un modelo farmacoeconómico a partir de datos obtenidos de un estudio prospectivo, multicéntrico, observacional realizado en España (Estudio Recover). Los pacientes del estudio habían desarrollado un acontecimiento adverso (AA) asociado a un ITIAN que motivaba su suspensión. En el análisis se incluyen todos los costes derivados de la toxicidad inducida por los ITIAN en los tratamientos antirretrovirales durante un año. Los costes (valores del año 2005) incluidos han sido: médicos directos (fármacos y manejo de AA) e indirectos (pérdidas de productividad). La estimación de los recursos relacionados con el manejo de los AA se ha realizado a través de un panel de consenso de expertos clínicos. Resultados. El incremento en el uso y coste de recursos sanitarios se correlaciona con la gravedad de todos los AA evaluados. El coste promedio total estimado por paciente ha sido de 4.012 €: 1.789 € por costes farmacológicos (ITIAN asociados con la discontinuación de la terapia por AA) y 2.223 € por costes directos e indirectos del manejo de los AA (45 y 55%, respectivamente, de los costes totales). El 73% de los costes por paciente asociados a AA se deben a la lipoatrofia (560 €), lipodistrofia mixta (535 €) y neuropatía periférica (533 €). Conclusión. En pacientes que desarrollan toxicidades asociadas a ITIAN, el coste económico de su manejo es superior al coste de adquisición de los ITIAN y produce un incremento significativo en los costes totales del tratamiento de la infección por VIH-1. El coste del manejo de estas toxicidades debería tenerse en cuenta en el diseño de estrategias de tratamiento antirretroviral más eficientes (AU)

Objective. To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV-1-infected patients. Methods. A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians. Results. The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 €, which included 1789 € in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 € in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 €), lipodystrophy (535 €) and peripheral neuropathy (533 €). Conclusion. Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies (AU)

[Errors in the diagnosis of acute viral hepatitides]. / Pomylky v diahnostytsi hostrykh virusnykh hepatytiv.

Errors have been analyzed in the diagnosis of acute viral hepatitides on the basis of the experience gained by the infectious clinic. The errors, illustrated by concrete examples, were found to be made because of underestimation of the existing symptoms, don't-care attitude to examination of the patient, misinterpreting results of laboratory tests or instrumental investigations. Ways have been outlined to remove errors in the differential diagnosis of acute viral hepatitides.

Preventive therapy with isoniazid. Cost-effectiveness of different durations of therapy.

Daily administration of isoniazid for one year to persons infected with Mycobacterium tuberculosis is effective in considerably reducing the risk of disease. From a practical viewpoint, this approach to prevention is less than ideal because it results in considerable costs as health care providers monitor for possible hepatotoxic effects and because it is difficult to maintain compliance for 12 months. The efficacy and toxicity of isoniazid preventive therapy regimens of 12, 24, and 52 weeks' duration were recently assessed in a study conducted in Eastern Europe. We used data from this study to conduct a cost-effectiveness analysis of the three alternative regimens. The results indicate that over a wide range of assumptions, a regimen of 24 weeks' duration is more cost-effective than either the 12- or 52-week regimen. Using base case estimates, the cost per case prevented for the 24-week regimen was $7,112, compared with $16,024 for the 52-week regimen. Among a cohort of 1,000 persons treated, each additional case prevented by the 52-week regimen would cost $80,807. Thus, a shorter course of isoniazid preventive therapy is relatively cost-effective compared with current policy.