Incidence and clinical characteristics of herpes zoster after lung transplantation.

BACKGROUND: Solid-organ transplant recipients are at high risk for the development of herpes zoster. Epidemiologic data in lung transplant recipients are lacking. We determined the incidence and clinical characteristics of herpes zoster, and the risk factors for developing herpes zoster, after lung transplantation. METHODS: We retrospectively reviewed all adult (>18 years old) lung transplants performed at our institution between January 2001 and December 2005. Clinical characteristics of herpes zoster and potential risk factors associated with herpes zoster were assessed. RESULTS: Two hundred thirty-nine lung transplant recipients were included in the analysis. Median time of follow-up was 722 days (range 18 to 1,943 days). Thirty-five episodes of herpes zoster occurred in 29 patients, with a calculated incidence of 55.1 cases per 1,000 person-years of follow-up. The cumulative probability of herpes zoster was 5.8% at 1 year, 18.1% at 3 years and 20.2% at 5 years post-transplant. Only 2 of the 35 (5.7%) patients had disseminated cutaneous infection and none had visceral involvement. Recurrence of herpes zoster was seen in 13.8% of patients. Post-herpetic neuralgia was detected in 20% of cases. Anti-viral prophylaxis, primarily for cytomegalovirus (CMV), was protective against herpes zoster. No significant epidemiologic risk factors associated with herpes zoster could be identified. CONCLUSIONS: Herpes zoster is a common complication after lung transplantation with a peak incidence at between 1 and 4 years post-transplant. Preventive strategies would be beneficial for this population.

Prevención de la transmisión sexual del VIH en adolescentes

En una muestra de 119 estudiantes de cuarto de Educación Secundaria Obligatoria (ESO) y primerode Bachillerato (52,6% mujeres) se analizan los conocimientos sobre la prevención de latransmisión sexual del virus del sida, las expectativas de resultados y de autoeficacia respecto a losmétodos preventivos y el tipo de prevención utilizada durante la última relación sexual. Para evitarlas respuestas inducidas respecto a los comportamientos preventivos se emplea un formato de preguntaabierta. Los resultados muestran que sólo el 23,5% de los estudiantes han dado dos respuestastotalmente correctas sobre estrategias consideradas eficaces en la prevención sexual del VIH:uso del preservativo y abstinencia (por este orden). El 70,5% valoran totalmente o muy eficaz elpreservativo para evitar la transmisión sexual del VIH y el 95% de los que dan la segunda respuestajuzgan totalmente eficaz la práctica de la abstinencia con la misma finalidad. En el caso del preservativose sienten totalmente o muy capaces de usarlo el 64,3%, mientras que cuando se trata de laabstinencia sólo se perciben con esa competencia el 20%. Por lo que se refiere al uso autoinformadode métodos preventivos en la última relación, por parte de los 29 estudiantes que tuvieronactividad sexual durante el mes anterior, se observa que 21 de ellos emplearon el preservativo, dosla píldora anticonceptiva, otros dos no precisan el tipo de precaución y el resto no tomó ninguna.Tanto el reducido nivel de conocimientos sobre prevención, como la baja percepción de autoeficaciapara mantenerse abstinentes, nos alertan sobre la necesidad de hacer un mayor esfuerzo de informaciónpara eliminar creencias equivocadas, como por ejemplo: sobre la pretendida eficacia protectorade tener relaciones sexuales con una pareja estable o conocida. Así mismo, conviene insistiren el uso del preservativo como anticonceptivo de elección entre los adolescentes

Adjuvant intra-arterial hepatic fotemustine for high-risk uveal melanoma patients.

Uveal melanoma metastases occur most commonly in the liver. Given the 50% mortality rate in patients at high risk of developing liver metastases, we tested an adjuvant intra-arterial hepatic (i.a.h.) chemotherapy with fotemustine after proton beam irradiation of the primary tumour. We treated 22 high-risk patients with adjuvant i.a.h. fotemustine. Planned treatment duration was 6 months, starting with four weekly doses of 100 mg/m(2), and after a 5-week rest, repeated every 3 weeks. The survival of this patient group was compared with that of a 3 : 1 matched control group randomly selected from our institutional database. Half of the patients experienced > or =grade 3 hepatotoxicity (one patient developing cholangitis 8 years later). Catheter-related complications occurred in 18%. With a median follow-up of 4.6 years for the fotemustine group and 8.5 years for the control group, median overall survival was 9 years [95% confidence interval (CI) 2.2-12.7] and 7.4 years (95% CI 5.4-12.7; P=0.5), respectively, with 5-year survival rates of 75 and 56%. Treatment with adjuvant i.a.h. fotemustine is feasible. However, toxicities are important. Although our data suggest a survival benefit, it was not statistically significant. Confirming such a benefit would require a large, internationally coordinated, prospective randomized trial.

Comparison of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin.

PURPOSE: To compare the efficacy of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin. METHODS: A randomized, prospective, single-masked study was conducted on 19 patients with culture-proven colonization of bacteria on the lid margins. Ophthalmic eligibility criteria included the presence of > or =50 colony-forming units/mL (CFU/mL) of bacteria on both right and left lids. Each patient received one drop of ofloxacin in one eye every night for one week, followed by one drop once a week for one month. In the same manner, each patient received bacitracin ointment (erythromycin or gentamicin ointment if lid margin bacteria were resistant to bacitracin) to the lid margin of the fellow eye. Quantitative lid cultures were taken at initial visit, one week, one month, and two months. Fifteen volunteers (30 lids) served as controls. Lid cultures were taken at initial visit, one week, and one month. RESULTS: Both antibiotic drop and ointment reduced average bacterial CFU/mL at one week and one month. Average bacterial CFU/mL reestablished to baseline values at two months. There was no statistically significant difference between antibiotic drop and ointment in reducing bacterial colonization on the lid margin. CONCLUSION: Antibiotic drops placed in the conjunctival cul-de-sac appear to be as effective as ointment applied to the lid margins in reducing bacterial colonization in patients with > or =50 CFU/mL of bacteria on the lid margins.

A mixed approach for proving non-inferiority in clinical trials with binary endpoints

When a new treatment is compared to an established one in a randomized clinical trial, it is standard practice to statistically test for non-inferiority rather than for superiority. When the endpoint is binary, one usually compares two treatments using either an odds-ratio or a difference of proportions. In this paper, we propose a mixed approach which uses both concepts. One first defines the non-inferiority margin using an odds-ratio and one ultimately proves non-inferiority statistically using a difference of proportions. The mixed approach is shown to be more powerful than the conventional odds-ratio approach when the efficacy of the established treatment is known (with good precision) and high (e.g. with more than 56% of success). The gain of power achieved may lead in turn to a substantial reduction in the sample size needed to prove non-inferiority. The mixed approach can be generalized to ordinal endpoints.

Biodiversitat de coleòpters i el seu paper com a plagues i com a agents de control biològic en un conreu de cítrics ecològics

El present treball estudiarà la comunitat d’espècies Coleoptera d’un camp de cítrics situat a la Selva de Camp, Tarragona, durant el període de temps dels anys 2002 fins al 2011. Els Coleoptera és l’ordre animal conegut comunament com els “escarabats” i és el més abundant i variat de tot el regne animal. Els estudis realitzats són pocs i, normalment, de les espècies més abundants (sobretot la família Coccinellidae). Totes les espècies d’aquest ordre presenten unes característiques típiques (García et al., 1989). (1) Presenten una cutícula dura, rígida i quitinitzada, amb el primer parell d’ales endurides (èlitres). Gran protecció als traumes físics. (2) Tenen una gran capacitat per retenir la humitat degut a que els estigmes s’obren els èlitres i eviten la pèrdua d’aigua per transpiració. (3) Presenten mandíbules mastegadores, adaptables i utilitzables per a una gran varietat de funcions (Chinery, 1988). (4) Algunes espècies poden acumular substàncies tòxiques a l’organisme. Presenten un règim alimentari fitòfag o micòfag, per norma general, tot i que també es poden trobar espècies sapròfagues o depredadores. És per aquest motiu que les espècies de Coleoptera podrien presentar un paper important com a potencial plagues o com a possible control biològic (Zahradnik, 1990). Durant moltes dècades, els plaguicides han constituït una lluita química contra les plagues dels cultius agrícoles, obtenint molt bons resultats en quant a manteniment i qualitat de les collites. No obstant, la seva utilització deliberada ha constituït en molts casos una important font de contaminació del territori. La seva gran mobilitat i persistència ha originat efectes de bioacumulació i biomagnificació a les xarxes tròfiques dels essers vius presents en aquestes zones. Actualment, per evitar tots aquests problemes ocasionats pels productes sintètics, el control biològic de plagues constitueix un dels principals pilars de la protecció moderna de cultius (Jacas et al., 2005). Se sap que les formigues tenen un doble rol molt important a les comunitats vegetals (poden ser mutualistes o depredadors generalistes), fent que la presència o absència d’aquestes pugui tenir efectes potencials sobre l’abundància d’altres artròpodes (James et al., 1999). És per aquest motiu que al present treball es realitzen experiments amb dos tipus d’arbres, els que presenten formigues i els que les formigues s’han exclòs experimentalment. Així doncs, els objectius del present treball són: - Descriure quantitativament la Comunitat de Coleoptera no Coccinellidae. - Descriure els canvis que s’han produït en la comunitat de Coleoptera al llarg de 10 anys. - Valorar la importància de les diferents espècies i/o famílies com a components de la biodiversitat d’un conreu ecològic. - Descriure els efectes sobre la comunitat de Coleoptera no Coccinellidae de la presència o absència de formgiues. - Valorar la importància de les diferents espècies i/o famílies com a possibles plagues o com a agents de control biològic.

The interior designer : Can the physiological agents of homeostasis create the appearance of design in nature?

Review of the book: The Tinkerer's Accomplice: How Design Emerges From Life Itself by J. Scott TurnerHarvard University Press: 2007. 304 pp.

Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients.

Steady state plasma concentrations of the (L)- and (D)-enantiomers of trimipramine (TRI), desmethyltrimipramine (DTRI), 2-hydroxytrimipramine (TRIOH) and 2-hydroxydesmethyl-trimipramine (DTRIOH) were measured in 27 patients receiving between 300 and 400 mg/day racemic TRI. The patients were phenotyped with dextromethorphan and mephenytoin, and the 8-hour urinary ratios of dextromethorphan/dextrorphan, dextromethorphan/3-methoxymorphinan, and (S)-mephenytoin/(R)mephenytoin were used as markers of cytochrome P-450IID6 (CYP2D6), CYP3A4/5 and CYP2C19 activities, respectively. One patient was a CYP2D6 and one was a CYP2C19 poor metabolizer. A stereoselectivity in the metabolism of TRI has been found, with a preferential N-demethylation of (D)-TRI and a preferential hydroxylation of (L)-TRI. CYP2D6 appears to be involved in the 2-hydroxylation of (L)-TRI, (L)DTRI and (D)-DTRI, but not of (D)-TRI, as significant correlations were measured between the dextromethorphan/dextrorphan ratios and the (L)-TRI/(L)-TRIOH (r = 0.45, p = 0.019), the (L)-DTRI/(L)-DTRIOH (r = 0.47, p = 0.014), and the (D)-DTRI/(D)-DTRIOH (r = 0.51, p = 0.006), but not with the (D)-TRI/(D)-TRIOH ratios (r = 0.29, NS). CYP2C19, but not CYP2D6, appears to be involved in the demethylation pathway, with a stereoselectivity toward the (D)-enantiomer of TRI, as a significant positive correlation was calculated between the mephenytoin (S)/(R) ratios and the concentrations to dose-to-weight ratios of (D)-TRI (r = 0.69, p = 0.00006). CYP3A4/5 appears to be involved in the metabolism of (L)-TRI to a presently not determined metabolite. The CYP2D6 poor metabolizer had the highest (L)-DTRI and (D)-DTRI concentrations to dose-to-weight ratios, and the CYP2C19 poor metabolizer had the highest (L)-TRI and (D)-TRI concentrations to dose-to-weight ratios of the group.

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma.

We present the long-term results of 18 chemotherapy relapsed indolent (N = 12) or transformed (N = 6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, (131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.

Agents de salut a l’àmbit penitenciari

Actualment el grup d’Addiccions veu la necessitat de seguir abordant el consum de drogues als nostres centres des de l’educació per a la salut i la reducció de danys, però també des de la capacitació personal. Per tal que tot això sigui una realitat, partim de l’Enquesta Estatal sobre Drogues entre els Internats a Presó (ESDIP, 2006). Aquesta evidencia que, per una banda, actualment es duen a terme als centres penitenciaris pràctiques de risc d’infecció per VIH, tant pel que fa a conductes d’injecció, sexuals o de realització de tatuatges, però, per altra banda, també posa de manifest el pobre coneixement de les vies de transmissió de l’VIH/SIDA i de l’hepatitis C, molt sovint ple de mites i/o creences errònies. L’ESDIP destaca el consum o l’abús de les drogues com un factor previ i paral·lel a la presó. La relació entre presó i drogues es produeix en dos dimensions que sovint es confonen, ja que no solament hi ha un problema d’ordre penal sinó també d’ordre social. Per una part, els delictes comesos per un alt percentatge de la població penitenciària estan relacionats amb la venda i/o consum de substàncies il·legals; i, per una altra banda, un nombre elevat d’interns té problemes personals, socials i de salut associats al consum de drogues, des de la pròpia dependència a greus malalties. Els programes de reducció de danys que s’han dut a terme tradicionalment s’han d’adaptar als nous perfils de consumidor; a les noves drogues i a les diferents vies d’administració. S’ha de tenir present que la major part dels problemes associats a l’activitat delictiva són d’índole psicosocial i no es restringeixen als consums problemàtics. Entre els interns podem trobar persones fàcilment influenciables, que presenten baixa tolerància a la frustració, poca capacitat per generar alternatives en situacions de conflicte, dificultats per gestionar el temps d’oci, baixa o nul·la escolarització, mancances a nivell psicoafectiu,

Oestrogen replacement treatment and the risk of endometrial cancer : an assessment of the role of covariates

The relationship between oestrogen replacement treatment and the risk of endometrial cancer was analysed in a case-control study of 158 histologically confirmed incident cases below the age of 75 and 468 controls in hospital for acute, non-neoplastic, non-hormone-related conditions conducted in the Swiss Canton of Vaud in 1988-1992. Overall, 60 (38%) cases vs. 93 (20%) controls had ever used oestrogen replacement treatment: the corresponding multiple logistic regression relative risk (RR) was 2.7 (95% confidence interval, CI: 1.7-4.1). The risk was directly related to duration of use, and rose to 5.1 (95% CI: 2.7-9.8) for > 5 year-use. The RR was still significantly elevated 10 or more years after stopping use (RR = 2.3, 95% CI: 1.2-4.5). When the role of covariates was considered, a significant interaction was observed with body mass index (RR for long-term oestrogen use = 6.0 for lean or normal weight women vs. 2.4 for overweight women). There was also a hint of a negative interaction with oral contraceptive (OC) use, since the RR for oestrogens was higher (or restricted) to women who had never used OC (RR = 5.4, for long-term oestrogen use), as compared with those who had used OC, who showed no significant evidence of association with oestrogens (RR = 0.9 for long-term use). There was no significant interaction with cigarette smoking. Thus, this study confirms the presence of a strong association between oestrogen replacement treatment and endometrial cancer risk, since in the late 1980s or early 1990s about 25% of cases could be attributed to oestrogen replacement treatment in this Swiss population. Further, it confirms the presence of significant negative interactions of oestrogen use with obesity, and, possibly, with OC as well.

Single-dose oral amoxicillin or linezolid for prophylaxis of experimental endocarditis due to vancomycin-susceptible and vancomycin-resistant Enterococcus faecalis.

Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter-induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID(90)]) or with 10 times the ID(90) of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID(90) and 10 times the ID(90). In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.