[Association between hematopoietic stem cell transplantation and Parsonage Turner syndrome: coincidence or cause-effect relationship?] / Asociación de trasplante de progenitores hematopoyéticos y síndrome de Parsonage-Turner: ¿coincidencia o relación causa-efecto?

Parsonage-Turner syndrome or idiopathic brachial neuritis is a total or partial inflammation of the brachial plexus, with a typical presentation as a sudden and very intense pain in the shoulder, followed by weakness and early amyotrophy. The etiology is still unknown, although an immune mediated mechanism is thought to be involved. Hematopoietic stem cell transplantation is a well-established treatment for hematological malignancies, but with a growing implication in the treatment of autoimmune diseases. The neurological side effects are probably underdiagnosed. The association of the Parsonage-Turner syndrome and the hematopoietic stem cell transplantation is scarce. We describe two clinical cases of idiopathic brachial plexopathy after hematopoietic stem cell transplantation. The reconstruction of the immune system after a transplant may be the trigger of a brachial plexopathy, but more studies are necessary for the etiology of this disease to be understood and to establish a cause-effect relation with the transplant.

Hepatitis tóxica tras tratamiento concomitante con interferón beta y aloe vera en un paciente con esclerosis múltiple: a propósito de un caso / Toxic hepatitis after concomitant interferon beta and aloe vera treatment in a patient with multiple sclerosis: A case report

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Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI.

A Phase I interventional Clinical Trial was performed with a potential tuberculosis vaccine, based on detoxified cellular fragments of M. tuberculosis, named RUTI. The objective was to evaluate the safety profile and T-cell immune responses over a 6-month period following subcutaneous inoculation. The double-blind, randomized and placebo-controlled trial was conducted in healthy volunteers, all recruited at one site. RUTI, at each of the four tested doses, starting from 5microg and going up to 200microg, and placebo were inoculated to groups of 4 and 2 volunteers respectively, consecutively. RUTI appeared to be well tolerated as judged by local and systemic clinical evaluation, though vaccine dose dependent local adverse reactions were recorded. T-cell responses of blood lymphocytes to PPD and a number of antigen subunits were elevated, when compared with controls subjects. These results support the feasibility of future evaluation, to be targeted at subjects with latent tuberculosis infection (LTBI).

Multiple drug interactions - induced serotonin syndrome: a case report.

Serotonin syndrome is a potentially life-threatening disorder of excessive serotoninergic activity often due to drug interactions. We report a case of serotonin syndrome induced by pharmacokinetic and pharmacodynamic interactions between three different selective serotonin-reuptake inhibitors (SSRI) and possibly ciprofloxacin. Extreme caution is necessary in patients treated with serotonin-reuptake inhibitors who need to be switched to another antidepressant or when they require the addition of concomitant drugs, especially serotoninergic drugs and isoenzimes of cytochrome P450 inhibitors.

The tuberculin skin test increases the responses measured by T cell interferon-gamma release assays.

RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.

Fate of the abstracts presented at three Spanish clinical pharmacology congresses and reasons for unpublished research.

OBJECTIVES: To assess the publication rate of abstracts at 5 years after their presentation at three consecutive clinical pharmacology congresses and to examine the reasons relating to the lack of publication. METHODS: Oral and poster presentations from the congresses of the Spanish Society of Clinical Pharmacology (SSCP) in 1994, 1996, and 1998 were reviewed. Authors were contacted to determine the fate of their presented studies and the reasons for not publishing them. Publications of abstracts with unknown fate were searched the in PubMed database. Determinants of publication were examined by Cox regression. RESULTS: In all, 248 abstracts were analysed. The cumulative publication rate at 5 years was 26%, and the median time for publication was 18 months (range: 2-60). The European Journal of Clinical Pharmacology was the English language medical journal where most abstracts were published. The median impact factor of the articles published was 1.96 (range: 0.29-8.32). The author survey identified a lack of time (38.2%) and a lack of interest (33.3%) as the main reasons for failure to publish. The only predictor of an abstract's publication was to be affiliated with a university department (hazard ratio: 1.98, 95% confidence interval: 1.20-3.27). CONCLUSIONS: Only one-quarter of the abstracts presented at SSCP congresses were subsequently published. A lack of time and interest were the main reasons given for not submitting these presentations for publication. Authors, scientific societies and editorial boards should enhance publications as full papers in peer-reviewed journals of the abstracts presented at meetings.

Antitumor necrosis factor-induced neutropenia: a case report with double positive rechallenges.

A 50-year-old man with ankylosing spondylitis who developed neutropenia after treatment of etanercept, with two positive rechallenges, and after the first infliximab infusion, is described. Although leukopenia and neutropenia related to etanercept and infliximab have been described as rare adverse events from clinical trials data, their mechanism of action are unknown. This patient developed recurrent mild neutropenia after exposition of two different antitumor necrosis factors; therefore, it seems to be an adverse reaction related to the therapeutic group. Doctors should be aware of this potentially severe adverse effect in patients treated with antitumor necrosis factor.

Analgesics for pain after traumatic or orthopaedic surgery: what is the evidence--a systematic review.

OBJECTIVE: To assess analgesic drugs in the treatment of postoperative pain after traumatic and orthopaedic surgery (TOS). DESIGN: A systematic review of randomised clinical trials (RCTs). DATA SOURCES: Electronic PubMed, EMBASE, The Cochrane Library, and hand searches. STUDY SELECTION: RCTs of analgesics administered by oral, intramuscular, intravenous, subcutaneous or rectal route, were compared to other analgesics or placebo, in patients under TOS. Study design, characteristics of the study population, analgesic drugs tested, pain intensity and pain relief scores, and adverse effects were assessed. RESULTS: Ninety-two RCTs (9,596 patients) met our inclusion criteria. Forty-two (46%) were placebo-controlled, and 50 (54%) were direct comparisons between non-opioid, opioid, and/or combinations of both. Patients' mean age (SD) was 49 years (18). In most trials, gastrointestinal ulcer, liver and renal diseases were exclusion criteria. Only 30 trials (33%) were double-blind and reported standardised outcomes of pain intensity and pain relief; 19 of these were single-dose, and follow up of analgesic effects lasted no more than 12 h in 23 (77%). Globally, only nine trials (10%) were double blind, described dropouts or withdrawals, performed analysis by intention to treat, and reported the effects magnitude. CONCLUSION: Evidence from RCTs on the treatment of postoperative pain after TOS is inadequate for clinical decision making. Assessment of analgesics in pain after TOS should be based on agreed clinically relevant outcomes, in representative patients, and for longer observation periods. In addition, it should include direct comparisons between candidate drugs or their combinations and between various drug administration schedules.

[Screening and effectiveness evaluation of a brief intervention in risk drinkers seen in primary health care]. / Evaluación del cribado y la efectividad de una intervención breve en bebedores de riesgo atendidos en consultas de atención primaria.

AIMS: To evaluate the screening, the effectiveness of an antialcoholic brief intervention for risk drinkers, the acceptation level to participate in this study, and the analytical parameters evolution associated to the alcohol consumption after of the intervention. DESIGN: Longitudinal prospective intervention study of 1 year of duration. SETTING: 5 urban primary care physician's practices. PARTICIPANTS: Of an aleatory pattern of 681 patients, men and women of 18-65 years old, were selected 78 risk drinkers. Patients with exclusion criteria (n=10), didn't wanted to participate (n=24) and had suspicion of alcoholic dependence syndrome (ADS) (n=11), didn't participated in this intervention. INTERVENTIONS: Were offered antialcoholic brief counselling with written supporter and were followed with alcohol consumption rate and analytical control at 2 and 12 months. MAIN MEASURES: Was estimated the prevalence of risk drinkers, the acceptation level to participate in this study, alcohol consumption and risk drinkers decreased at 2 and 12 months, analytical parameters evolution after of the intervention. RESULTS: Prevalence of risk drinkers: 11.5% (95% confidence interval [CI], 8.3%-14.7%). Acceptation level to participate in this study: 64.7%. Significative alcohol consumption decreased at 2 and 12 months (P<.05). Risk drinkers decreased: at 2 months were 57.6% (95% CI, 50.3%-64.9%; P=.01) and at 12 months were 42.4% (95% CI; 35.9%-48.9%) (P=.003). GGT, MCV, cholesterol, and triglycerides significative decreased. CONCLUSIONS: Low prevalence of risk drinkers without suspicion of ADS in our setting; high effectiveness of antialcoholic brief counselling and high acceptation level to participate in this study; reduction of the GGT, MCV, cholesterol, and triglycerides after of the intervention.

Evaluación del cribado y la efectividad de una intervención breve en bebedores de riesgo atendidos en consultas de atención primaria / Screening and effectiveness evaluation of a brief intervention ub risk drinkers seen in primary health care

Objetivos. Evaluar el cribado y la efectividad de una intervención breve antialcohólica, el grado de aceptación y la evolución de los parámetros biológicos asociados con el consumo de alcohol tras la intervención. Diseño. Estudio prospectivo longitudinal de intervención de 1 año de duración. Emplazamiento. Cinco consultas de atención primaria urbanas. Participantes. De una muestra aleatoria de 681 sujetos de ambos sexos y de edad de 18-65 años, se seleccionó a 78 bebedores de riesgo. Los que cumplían criterios de exclusión (n = 10), no aceptaban participar (n = 24) y presentaban sospecha de síndrome de dependencia alcohólica (n = 11) no participaron en el estudio. Intervenciones. Se ofrecía un breve consejo antialcohólico apoyado con soporte escrito, y se realizaba un seguimiento a los 2 y 12 meses mediante la cuantificación del consumo de alcohol y un control analítico. Mediciones principales. Se estimó la prevalencia de bebedores de riesgo, el grado de aceptación a participar en el estudio, la disminución del consumo de alcohol y de bebedores de riesgo a los 2 y 12 meses, y la evolución de los parámetros analíticos tras la intervención. Resultados. La prevalencia de bebedores de riesgo fue del 11,5% (intervalo de confianza [IC] del 95%, 8,3-14,7%). El grado de aceptación a participar en el estudio fue del 64,7%. Se observó un decremento significativo (p < 0,05) en el consumo de alcohol a los 2 y 12 meses, así como una disminución de los bebedores de riesgo, que a los 2 meses fue del 57,6% (IC del 95%, 50,3-64,9%; p = 0,01) y a los 12 meses del 42,4% (IC del 95%, 35,9-48,9%; p = 0,003). Asimismo, se produjeron disminuciones significativas en las concentraciones de GGT, VCM, colesterol y triglicéridos. Conclusiones. Se observa una baja prevalencia de bebedores de riesgo sin sospecha de síndrome de dependencia alcohólica en nuestro medio, así como una elevada efectividad del consejo breve antialcohol y del grado de aceptación a participar en el estudio. Se apreció una disminución de las concentraciones de GGT, VCM, colesterol y triglicéridos tras la intervención

Aims. To evaluate the screening, the effectiveness of an antialcoholic brief intervention for risk drinkers, the acceptation level to participate in this study, and the analytical parameters evolution associated to the alcohol consumption after of the intervention. Design. Longitudinal prospective intervention study of 1 year of duration. Setting. 5 urban primary care physician's practices. Participants. Of an aleatory pattern of 681 patients, men and women of 18-65 years old, were selected 78 risk drinkers. Patients with exclusion criteria (n=10), didn't wanted to participate (n=24) and had suspicion of alcoholic dependence syndrome (ADS) (n=11), didn't participated in this intervention. Interventions. Were offered antialcoholic brief counselling with written supporter and were followed with alcohol consumption rate and analytical control at 2 and 12 months. Main measures. Was estimated the prevalence of risk drinkers, the acceptation level to participate in this study, alcohol consumption and risk drinkers decreased at 2 and 12 months, analytical parameters evolution after of the intervention. Results. Prevalence of risk drinkers: 11.5% (95% confidence interval [CI], 8.3%-14.7%). Acceptation level to participate in this study: 64.7%. Significative alcohol consumption decreased at 2 and 12 months (P<.05). Risk drinkers decreased: at 2 months were 57.6% (95% CI, 50.3%-64.9%; P=.01) and at 12 months were 42.4% (95% CI; 35.9%-48.9%) (P=.003). GGT, MCV, cholesterol, and triglycerides significative decreased. Conclusions. Low prevalence of risk drinkers without suspicion of ADS in our setting; high effectiveness of antialcoholic brief counselling and high acceptation level to participate in this study; reduction of the GGT, MCV, cholesterol, and triglycerides after of the intervention

Medical speciality and pattern of medicines prescription.

OBJECTIVE: To describe the prescribing patterns and their quality in relation to the prescriber's medical specialty in a defined population. METHODS: The study was done on a random sample of all primary care medical prescriptions made through the social security system during 1 year in Andorra, a small European country. Number and type of prescribed medicines, prescribers' medical speciality and patients' age and gender were recorded. Medical specialties considered were General Practice, Paediatrics, Cardiology, Pneumology, Gynaecology, Ophthalmology and Other. A set of various quality indicators [World Health Organisation (WHO)/International Network for Rational Use of Drugs (INRUD) indicators and others] was used. RESULTS: The number of medicines prescribed per encounter varied depending on the prescriber's medical specialty and patient's age. Cardiologists and pneumologists tended to prescribe more medicines than other medical specialties. Patients older than 65 years received more prescriptions than younger adults, mostly at the expense of cardiovascular drugs. The contribution of the various groups and subgroups of medicines and the scores of various prescribing indicators showed wide variability across the medical specialties. CONCLUSION: Prescribing patterns and indicators of prescription quality show wide variability depending on the prescriber's medical specialty. This has important implications for priority setting in information, continuous education and research.

Oral antispastic drugs in nonprogressive neurologic diseases: a systematic review.

OBJECTIVE: To assess the efficacy of oral drugs in the treatment of spasticity in patients with nonprogressive neurologic disease (NPND). METHODS: Systematic review of double-blind randomized controlled trials of antispastic oral drugs in the treatment of spasticity in NPND. DATA SOURCES: Electronic MEDLINE, PubMed, Cochrane Library, and hand searches. RESULTS: Twelve studies (469 patients) were included (6 on stroke, 3 on spinal cord diseases, and 3 on cerebral palsy). Tizanidine was assessed in four trials (276 patients, 142 exposed), dantrolene in four (103, 93), baclofen in three (70, 55), diazepam in two (127, 76), and gabapentin in one (28, all exposed). Most trials were of small size, of short duration, and their methodologic quality was inadequate. Ten trials were controlled with placebo and only two were direct comparisons between drugs. Efficacy outcome variables were heterogeneous. Only four reports described the magnitude of the antispastic effect. The incidence of adverse drug effects (drowsiness, sedation, and muscle weakness) was high. CONCLUSION: Evidence on the efficacy of oral antispastic drugs in NPND is weak and does not include evaluation of patients' quality of life. If any, efficacy is marginal. Adverse drug reactions were common. Better methodologic instruments are needed for the evaluation of antispastic treatment.

Prescribing information in 26 countries: a comparative study.

This study was set up to document the variability of prescribing information from different sources concerning indications, side effects and cautions of selected drugs. An original method to measure the degree of information agreement among different written materials, such as summaries of product characteristics, package inserts and data sheets, and a widely accepted reference text was developed. The results show that there is substantial disagreement in the materials available to prescribers and patients in different countries. Disagreement was even found within a single country when written materials from different brands of the same drug were compared. The discordance can be explained by the fact that the evidence available for each drug is considered/assessed differently by separate countries. It is argued that the discrepancies found may mislead prescribers, patients and those comparing drug-use patterns across countries. National regulatory authorities have a key role to play in remedying this situation, and a two-pronged approach is proposed. At the international level, national authorities should strengthen collaboration and information interchange and, at the national level, should implement appropriate measures aimed at removing contradictory statements on drug-information materials that have no reason to be different. Finally, further training and continued education aimed at drug regulatory officials could provide the necessary knowledge and enable national authorities to meet the need for drug information that is independent of commercial interests.

[The evolution of use of anti-Parkinson drugs in Spain]. / Evolución del consumo de fármacos antiparkinsonianos en España.

INTRODUCTION: In recent years new anti Parkinson drugs have been marketed and there has been controversy over the safety of some drugs. OBJECTIVE: To analyze the evolution of the consumption of anti Parkinson drugs and the effect of the newer drugs. PATIENTS AND METHODS: A study of the consumption of anti Parkinson drugs (1989 1998). Data were obtained from the ECOM database of the Ministry of Health and TEMPUS of the National Statistics Institute. The drugs were classified using the Anatomo Therapeutic Clinical Classification (ATC). Consumption was expressed in defined daily dosage (DDD) and the costs in euros. The drugs marketed since 1990 were classified as new drugs and the others as classical drugs. RESULTS: The total consumption of drugs increased from 1.92 DDD/1,000 inhabitants/day in 1989 to 3.64 DDD/1,000 inhabitants/day in 1998. The drugs showing the greatest increase were selegiline, pergolide and levodopa. The total pharmaceutical expenses tripled. There was a smaller increase in the consumption of new drugs (1.2% of the total in 1991 and 6.6% in 1998) than in their costs (6.7% of the total in 1991 and 38.8% in 1998). The cost per DDD of the new drugs increased five times (1989: 2.55 euros and 1998: 13.59 euros) and that of the classical drugs was similar (1989: 0.54 euros and 1998: 0.62 euros). CONCLUSIONS: The total consumption of anti Parkinson drugs has progressively increased. The consumption of selegiline has also increased in spite of controversy over its safety. The new drugs have a major economic effect.

Evolución del consumo de fármacos antiparkinsonianos en España / The evolution of use of anti-parkinson drugs in spain

Introducción. En los últimos años se han comercializado nuevos fármacos antiparkinsonianos y ha existido una polémica sobre la seguridad de algunos de ellos. Objetivo. Analizar la evolución del consumo de los fármacos antiparkinsonianos y el impacto de los nuevos fármacos. Material y métodos. Estudio de consumo de los fármacos antiparkinsonianos (1989-1998). Los datos se obtuvieron de las bases ECOM, del Ministerio de Sanidad y Consumo, y TEMPUS, del Instituto Nacional de Estadística. Los fármacos se clasificaron mediante la Clasificación Anatómica-TerapéuticaQuímica (ATC). El consumo se expresó en dosis diarias definidas (DDD), y los costes, en euros (n). Los fármacos comercializados desde 1990 se clasificaron como nuevos fármacos, y el resto, como fármacos clásicos. Resultados. El consumo total de los fármacos aumentó desde 1,92 DDD/1.000 habitantes/día, en 1989, hasta 3,64 DDD/1.000 hab./día, en 1998. Los fármacos con un mayor incremento del consumo fueron selegilina, pergolida y levodopa. El coste farmacéutico total se triplicó. El aumento del consumo de los nuevos fármacos fue menor (1,2 por ciento del total en 1991 y 6,6 por ciento en 1998) que el de sus costes (6,7 por ciento del total en 1991 y 38,8 por ciento en 1998). El coste por DDD de los nuevos fármacos aumentó cinco veces (1989: 2,55n y 1998: 13,59n y el de los fármacos clásicos fue similar (1989: 0,54n y 1998: 0,62n). Conclusiones. El consumo total de fármacos antiparkinsonianos aumenta progresivamente. El consumo de selegilina también ha aumentado, a pesar de la polémica sobre su seguridad. Los nuevos fármacos tienen un gran impacto económico (AU)