Diagnosis of tuberculosis infection using interferon-γ-based assays

Interferon-γ-based assays, collectively known as IFN-γ release assays (IGRAs), have emerged as a reliable alternative to the old tuberculin skin test (TST) for the immunodiagnosis of tuberculosis (TB) infection. The 2 commercially available tests, the enzyme-linked immunosorbent assay (ELISA), QuantiFERON-TB Gold Intube (QFT-IT), and the enzyme-linked immunospot assay (ELISPOT), T-SPOT.TB, are more accurate than TST for the diagnosis of TB, since they are highly specific and correlate better with the existence of risk factors for the infection. According to the available data, T-SPOT.TB obtains a higher number of positive results than QFT-IT, while its specificity seems to be lower. Although the sensitivity of the IFN-γ -based assays may be impaired to some extent by cellular immunosuppression and extreme ages of life, they perform better than TST in these situations. Data from longitudinal studies suggest that IFN-γ-based tests are better predictors of subsequent development of active TB than TST; however this prognostic value has not been consistently demonstrated. This review focuses on the clinical use of the IFN-γ -based tests in different risk TB groups, and notes the main limitations and areas for future development.

Inhibition of nociceptive responses after systemic administration of amidated kyotorphin

BACKGROUND AND PURPOSE Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible clinical use of KTP as an analgesic. In this study, we aimed to increase the lipophilicity of KTP by amidation and to evaluate the analgesic efficacy of a new KTP derivative (KTP-amide - KTP-NH 2). EXPERIMENTAL APPROACH We synthesized KTP-NH 2. This peptide was given systemically to assess its ability to cross the BBB. A wide range of pain models, including acute, sustained and chronic inflammatory and neuropathic pain, were used to characterize analgesic efficacies of KTP-NH 2. Binding to opioid receptors and toxicity were also measured. KEY RESULTS KTP-NH 2, unlike its precursor KTP, was lipophilic and highly analgesic following systemic administration in several acute and chronic pain models, without inducing toxic effects or affecting motor responses and blood pressure. Binding to opioid receptors was minimal. KTP-NH 2 inhibited nociceptive responses of spinal neurons. Its analgesic effects were prevented by intrathecal or i.p. administration of naloxone. CONCLUSIONS AND IMPLICATIONS Amidation allowed KTP to show good analgesic ability after systemic delivery in acute and chronic pain models. The indirect opioid-mediated actions of KTP-NH 2 may explain why this compound retained its analgesic effects although the usual side effects of opioids were absent, which is a desired feature in next-generation pain medications

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.568.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 24 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 1230months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.57,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Compositional ideas in the bayesian analysis of categorical data with application to dose finding clinical trials

Compositional random vectors are fundamental tools in the Bayesian analysis of categorical data.Many of the issues that are discussed with reference to the statistical analysis of compositionaldata have a natural counterpart in the construction of a Bayesian statistical model for categoricaldata.This note builds on the idea of cross-fertilization of the two areas recommended by Aitchison (1986)in his seminal book on compositional data. Particular emphasis is put on the problem of whatparameterization to use

Influencia social y uso del preservativo en la prevención de la transmisión heterosexual del VIH = Social influence and condom use for VIH heterosexual transmission prevention

Se revisan diferentes formas en que la influencia social puede incidir sobre los comportamientosheterosexuales de prevención de la transmisión del VIH de los jóvenes y se presentanlos resultados de algunos trabajos de las autoras, así como de otros investigadores, en que seanalizan dichas relaciones. Se concluye resaltando: 1) la utilidad clínica de la evaluación de lasexpectativas de autoeficacia para poder intervenir específicamente en aquellas áreas en que losjóvenes se perciban con menores capacidades para ser preventivos, 2) la relación observadaentre el uso de preservativo autoinformado y la creencia en su aceptación por parte de los referentessociales más cercanos y 3) la conveniencia de que los jóvenes posean suficientes habilidadesde comunicación que les permitan negociar con éxito el uso del preservativo y les ayudena compensar posibles influencias sociales en contra de su empleo

Population based resource allocation: The use of hybrid risk adjustment

The emphasis on integrated care implies new incentives that promote coordinationbetween levels of care. Considering a population as a whole, the resource allocation systemhas to adapt to this environment. This research is aimed to design a model that allows formorbidity related prospective and concurrent capitation payment. The model can be applied inpublicly funded health systems and managed competition settings.Methods: We analyze the application of hybrid risk adjustment versus either prospective orconcurrent risk adjustment formulae in the context of funding total health expenditures for thepopulation of an integrated healthcare delivery organization in Catalonia during years 2004 and2005.Results: The hybrid model reimburses integrated care organizations avoiding excessive risktransfer and maximizing incentives for efficiency in the provision. At the same time, it eliminatesincentives for risk selection for a specific set of high risk individuals through the use ofconcurrent reimbursement in order to assure a proper classification of patients.Conclusion: Prospective Risk Adjustment is used to transfer the financial risk to the healthprovider and therefore provide incentives for efficiency. Within the context of a National HealthSystem, such transfer of financial risk is illusory, and the government has to cover the deficits.Hybrid risk adjustment is useful to provide the right combination of incentive for efficiency andappropriate level of risk transfer for integrated care organizations.