Predictive factors for functional failure of ventral mesh rectopexy in the treatment of rectal prolapse and obstructed defecation.

BACKGROUND: Ventral mesh rectopexy (VMR) is widely accepted for the treatment of rectal prolapse or obstructed defecation. However, despite good anatomical results, the improvement of functional symptoms (constipation or incontinence) cannot always be obtained and in some cases these symptoms may even worsen. The aim of the present study was to identify possible predictors of functional failure after VMR. METHODS: Data of all consecutive patients who had VMR for the treatment of rectal prolapse and/or obstructed defecation between January 2017 and December 2020 in three different pelvic floor surgical centres in Italy were analysed to identify possible predictors of functional failure, intended as persistence, worsening or new onset of constipation or faecal incontinence. Symptom severity was assessed pre- and postoperatively with the Wexner Constipation score and Obstructed Defecation Syndrome score. Quality of life was assessed, also before and after treatment, with the Patients Assessment of Constipation Quality of Life questionnaire, the Pelvic Floor Disability Index and the Pelvic Floor Impact Questionnaire. Faecal incontinence was evaluated with the Cleveland Clinic Incontinence Score. The functional outcomes before and after surgery were compared. RESULTS: Sixty-one patients were included (M:F ratio 3:60, median age 64 years [range 33-88 years]). Forty-two patients (68.9%) had obstructed defecation syndrome, 12(19.7%) had faecal incontinence and 7 patients (11.5%) had both. A statistically significant reduction between pre- and postoperative Obstructed Defecation Syndrome and Wexner scores was reported (p < 0.0001 in both cases). However, the postoperative presence of constipation occurred in 22 patients (36.1%) (this included 3 cases of new-onset constipation). The presence of redundant colon and the pre-existent constipation were associated with an increased risk of persistence of constipation postoperatively or new-onset constipation (p = 0.004 and p < 0.0001, respectively). The use of postoperative pelvic floor rehabilitation (p = 0.034) may reduce the risk of postoperative constipation. CONCLUSIONS: VMR is a safe and effective intervention for correcting the anatomical defect of rectal prolapse. The degree of prolapse, the presence of dolichocolon and pre-existing constipation are risk factors for the persistence or new onset of postoperative constipation. Postoperative rehabilitation treatment may reduce this risk.

Obstructed defecation syndrome associated with paradoxical puborectalis contraction: osteopathic treatment versus anal biofeedback. Results of a pilot study.

BACKGROUND: Biofeedback is the most widespread rehabilitative therapy for the treatment of anismus after failed conservative treatment. Osteopathy represents an alternative therapy for constipation. The aim of this study was to evaluate short- and long-term results of osteopathic treatment as compared to biofeedback in patients with dyssynergic defecation. METHODS: This was a prospective cohort pilot study on 30 patients with dyssynergic defecation enrolled at the Colorectal Clinic of the University Hospital of Ferrara, Italy, from May 2015 to May 2016 and followed until May 2020. Dyssynergic defecation was defined as the inappropriate contraction of the pelvic floor or less than 20% relaxation of basal resting sphincter pressure (on anal manometry) with adequate propulsive forces during attempted defecation. Dyssynergic patients were divide into 2 treatment groups: 15 patients had osteopathy and 15 patients had biofeedback. Before and 3 months after rehabilitation treatment, all patients had anorectal manometry, defecography, and ultrasound, and were evaluated with the Cleveland Clinic Florida (CCF) constipation score, obstructed defecation syndrome (ODS) score, Colo-rectal-anal Distress Inventory (CRADI-8), Colo-rectal-anal Impact Questionnaire (CRAIQ-7), and the Brusciano Score (BS). To evaluate the efficacy of osteopathy and biofeedback in the long-term, all patients completed the above-mentioned questionnaires 5 years later via a telephone interview. RESULTS: The two treatments were similarly effective in the short term with reduction in questionnaires scores, and increase in the percentage of anal sphincter release at straining at anorectal manometry in both groups. The ODS score was significantly reduced in biofeedback group (p = 0.021). The 3-month post-treatment BS was lower in the osteopathy group, but this just failed to reach statistical significance (p = 0.050). Periodic rehabilitation reinforcements were provided. The CCF constipation score decreased significantly in the osteopathy group (p = 0.023) after 5 years. CONCLUSIONS: Osteopathy is a promising treatment for dyssynergic defecation, and it can be associated with biofeedback.

Characterization of the phone-calls made to a poison center related to household and cosmetics products exposition in pediatrics. / Caracterización de las consultas realizadas a un Centro de Información Toxicológica por productos de aseo y productos cosméticos en niños.

INTRODUCTION: Household cleaning products and cosmetics are necessary for daily life and widely used by the population. However, their use may not be risk-free, especially when they are not used or stored as recommended. It is important to characterize exposures, as this is useful for developing stra tegies to reduce morbidity, mortality, and health costs associated, especially in the child population. OBJECTIVE: To describe reports associated with household cleaning products and cosmetics exposure in patients under the age of 12, reported to the Poison Information Center of the Catholic University of Chile (CITUC). PATIENTS AND METHOD: Descriptive cross-sectional study of phone calls to CITUC during 2016. The analyzed variables were age, sex, product, caller, caller and incident location, ex posure circumstances, exposure route(s), symptoms, and severity from manual records and from the WHO's electronic record software 'INTOX Data Management System'. RESULTS: 3,415 cases met the inclusion criteria. Children under the age of five represented 91% of the exposures, and 58.5% were male. 99.4% were accidental exposures, and 98.6% occurred at home. Family members (57%) and health personnel (42%) made the calls. 68.3% of the patients had no symptoms after exposure. The four products with the highest incidence were household bleach (27.6%), floor cleaners and polishers (13.1%), dish soap (7.9%), and perfume/cologne (5.8%). The main exposure route was by ingestion (89.4%). CONCLUSIONS: Household cleaning products and cosmetics are common causes of exposures especially in children under the age of five. Although these products have a low morbidity and mortality rate, it is important to educate the population to prevent possible poisonings in the child population.

Caracterización de las consultas realizadas a un Centro de Información Toxicológica por productos de aseo y productos cosméticos en niños / Characterization of the phone-calls made to a poison center related to household and cosmetics products exposition in pediatrics

INTRODUCCIÓN: Los productos de aseo y cosméticos son necesarios en el diario vivir y ampliamente utilizados por la población. Sin embargo, su uso puede no estar exento de riesgos, especialmente cuando no se utilizan o almacenan según lo recomendado. Es importante caracterizar las exposiciones, ya que eso es útil para implementar estrategias para reducir la morbilidad, mortalidad y costos asociados, especialmente en la población infantil. OBJETIVO: Caracterizar los reportes asociados a exposiciones a productos de aseo y productos cosméticos en pacientes menores de 12 años reportados al Centro de Información Toxicológica de la Universidad Católica de Chile (CITUC). PACIENTES Y MÉTODO: Estudio descriptivo transversal de llamados telefónicos reportados a CITUC durante el año 2016. Se analizaron las variables: edad, sexo, agente, interlocutor, localización del interlocutor e inciden te, circunstancia de exposición, vía(s) de exposición, sintomatología, y severidad, mediante fichas de registro manual y desde el software de registro electrónico denominado "INTOX Data Manage ment System" de la OMS. RESULTADOS: Cumplieron criterios de inclusión 3.415 casos. Los menores de 5 años representaron el 91% de las exposiciones y el 58,5% correspondió al sexo masculino. Un 99,4% correspondió a exposiciones accidentales y el 98,6% ocurrieron en el hogar. El 68,3% no presentó síntomas, tras la exposición. Las llamadas fueron realizadas por familiares (57%) y personal de salud (42%). Los 4 agentes con mayor incidencia fueron cloro doméstico (27,6%), limpiadores y lustres de pisos (13,1%), lavalozas (7,9%) y perfumes/colonias (5,8%). La principal vía de exposición fue digestiva (89,4%). CONCLUSIONES: Los productos de aseo y cosméticos son causas comunes de exposiciones especialmente en menores de 5 años. Si bien son productos de baja mortalidad y morbilidad, es importante educar a la población para prevenir posibles intoxicaciones en la población infantil.

INTRODUCTION: Household cleaning products and cosmetics are necessary for daily life and widely used by the population. However, their use may not be risk-free, especially when they are not used or stored as recommended. It is important to characterize exposures, as this is useful for developing stra tegies to reduce morbidity, mortality, and health costs associated, especially in the child population. OBJECTIVE: To describe reports associated with household cleaning products and cosmetics exposure in patients under the age of 12, reported to the Poison Information Center of the Catholic University of Chile (CITUC). PATIENTS AND METHOD: Descriptive cross-sectional study of phone calls to CITUC during 2016. The analyzed variables were age, sex, product, caller, caller and incident location, ex posure circumstances, exposure route(s), symptoms, and severity from manual records and from the WHO's electronic record software 'INTOX Data Management System'. RESULTS: 3,415 cases met the inclusion criteria. Children under the age of five represented 91% of the exposures, and 58.5% were male. 99.4% were accidental exposures, and 98.6% occurred at home. Family members (57%) and health personnel (42%) made the calls. 68.3% of the patients had no symptoms after exposure. The four products with the highest incidence were household bleach (27.6%), floor cleaners and polishers (13.1%), dish soap (7.9%), and perfume/cologne (5.8%). The main exposure route was by ingestion (89.4%). CONCLUSIONS: Household cleaning products and cosmetics are common causes of exposures especially in children under the age of five. Although these products have a low morbidity and mortality rate, it is important to educate the population to prevent possible poisonings in the child population.

Pharmacokinetics of levobupivacaine with epinephrine in transversus abdominis plane block for postoperative analgesia after Caesarean section.

BACKGROUND: Transversus abdominis plane block is increasingly used for post-Caesarean section analgesia. Cases of toxicity and the limited pharmacokinetic information during pregnancy motivated this study. The objective of the study was to characterise and compare the pharmacokinetics of levobupivacaine with epinephrine in tranversus abdominis plane block, in post-Caesarean section patients and healthy volunteers. METHODS: After approval by the Ethics Committee, we collected data from 12 healthy parturients after elective Caesarean section (Study 1) and data from 11 healthy male volunteers from a previous study (Study 2). Transversus abdominus plane block was performed under ultrasound guidance. The following injectates were used: levobupivacaine 0.25%, 20 ml with epinephrine 5 µg ml-1 (Study 1) per side; 20 ml of the same solution (unilateral block) (study 2). The plasma venous concentration of levobupivacaine was measured serially for 90 min. Pharmacokinetic parameters (volume of distribution, clearance, and absorption half-life) were estimated using a non-linear mixed effects model (NONMEM). Simulation in 1000 patients estimated the maximum concentration and the time to reach it after bilateral transversus abdominis plane block. RESULTS: Venous concentrations were below toxic levels (2.62 mg L-1). Levobupivacaine volume of distribution after Caesarean section was higher than in healthy volunteers [172 L (70 kg)-1 (95% confidence interval: 137-207) vs 94.3 L (70 kg)-1 (95% CI: 62-128); P<0.01]. Clearance and absorption half-life were similar. The simulation showed that maximum levobupivacaine concentration is lower and occurs later in postpartum patients (P<0.01). Postoperative analgesia was effective. CONCLUSIONS: Postpartum women reached relatively low plasma concentrations of levobupivacaine after transversus abdominal plane block given a volume of distribution 80% higher than volunteers, which could confer a greater margin of safety. CLINICAL TRIAL REGISTRATION: NCT02852720.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

BACKGROUND: Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. METHODS: Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. RESULTS: A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). CONCLUSIONS: We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. CLINICAL TRIAL REGISTRATION: NCT02557867.

Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study.

BACKGROUND: Per-oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established. AIM: To compare tacrolimus drug exposure after sublingual and oral administration in liver transplant recipients. METHODS: Experimental, open-label, non-randomised, cross-over study. Tacrolimus exposure was evaluated in 32 liver transplant recipients receiving oral administration. 12 h tacrolimus area-under-the-curve (AUC0-12 h ) was calculated using tacrolimus blood concentrations at 0-0.5-1-2-4-6-8-12 hrs post-dose. Recipients were switched to sublingual administration, and dose was adjusted to reach similar trough levels, new AUC0-12 h was calculated. Correlation between AUC0-12 h and trough levels was determined for both oral and sublingual phases. RESULTS: Similar trough levels were accomplished with oral and sublingual administration (6.68 ± 2 ng/mL vs. 6.62 ± 1.9 ng/mL (P = 0.8)). Although concentration 2 h post dose was higher in oral phase (15.36 ± 7.14 vs. 13.18 ± 5.64, P = 0.015), AUC0-12 h was similar in both phases (116.6 ± 34.6 vs. 111.5 ± 36.93 ng/mL* h, P = 0.19). Daily dose of tacrolimus required in sublingual phase was 37% lower than that used in oral phase (P < 0.0001), suggesting significantly increased bioavailability of tacrolimus when employing sublingual route. Good correlation between AUC0-12 h and trough levels was observed in sublingual phase (r2 = 0.74). Twenty-two recipients were maintained on sublingual administration after the end of study (mean follow-up: 18.7 ± 5.8 months). No difference in liver function tests or rejection rates was found during follow-up period. CONCLUSIONS: Sublingual administration of tacrolimus is feasible and provides similar drug exposure compared with oral administration. In our study, at long-term follow-up, sublingual administration was not associated with liver transplant rejection.

Rocuronium pharmacokinetics and pharmacodynamics in the adductor pollicis and masseter muscles.

BACKGROUND: The aim of this study was to characterize the dose-effect relationship of rocuronium at the adductor pollicis and masseter muscles. METHODS: Ten, ASA I, adult patients, received a bolus dose of rocuronium 0.3 mg/kg during propofol based anesthesia. Train-of-four (TOF) was simultaneously monitored at the masseter and the adductor pollicis muscles until recovery. Rocuronium arterial serum concentrations were measured during 120 min. The first twitch of the TOF response was used to characterize the time-effect profile of both muscles using pharmacokinetic-pharmacodynamic analysis in NONMEM. A decrease in NONMEM objective function (∆OFV) of 3.84 points for an added parameter was considered significant at the 0.05 level. RESULTS: Onset time at the masseter (mean ± SD, 1.5 ± 0.9 min) was faster than at the adductor pollicis (2.7 ± 1.4 min, P < 0.05). Recovery, measured as the time to TOF ratio = 0.9 was similar between muscles 29.9 ± 6.7 (adductor pollicis) vs. 29.3 ± 8.1 (masseter). (P = 0.77). The estimated pharmacodynamic parameters [mean (95% CI)] of the adductor pollicis muscle and the masseter muscle were; plasma effect-site equilibration half-time (teq) 3.25 (2.34, 3.69) min vs. 2.86 (1.83, 3.29) min, (∆OFV 383.665); Ce50 of 1.24 (1.13, 1.56) mg/l vs. 1.19 (1.00, 1.21) mg/l, (∆OFV 184.284); Hill coefficient of 3.97 (3.82, 5.62) vs. 4.68 (3.83, 5.71), (∆OFV 78.906). CONCLUSIONS: We found that the masseter muscle has faster onset of blockade and similar recovery profile than adductor pollicis muscle. These findings were best, explained by a faster plasma effect-site equilibration of the masseter muscle to rocuronium.

Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index.

BACKGROUND: I.V. lidocaine is increasingly used as an adjuvant during general anaesthesia. The aim of this study was to evaluate the effect of i.v. lidocaine in reducing propofol anaesthetic requirements during total i.v. anaesthesia (TIVA) maintenance and to evaluate its effect on early recovery from anaesthesia. METHODS: Forty adult patients undergoing elective laparoscopic cholecystectomy under TIVA were randomly allocated into the lidocaine group (administered 1.5 mg kg(-1) i.v. lidocaine over 5 min followed by 2 mg kg(-1) h(-1)) and the control group (administered an equal volume of saline). Propofol was administered using a target-controlled infusion to maintain the bispectral index values between 40 and 60. After surgery, all infusions were discontinued and the time to extubation was recorded. Serial arterial blood samples were drawn to assess drug plasma levels. RESULTS: The maintenance dose of propofol was significantly lower in the lidocaine group [6.00 (0.97) mg kg(-1) h(-1)] vs the control group [7.25 (1.13) mg kg(-1) h(-1); P=0.01]. Propofol plasma levels measured at the end of the infusion were 3.71 (0.89) µg ml(-1) in the lidocaine group and 3.67 (1.28) µg ml(-1) in the control group (P=0.91). The median time to extubation was longer (11.0 min; range: 10.0-21.0) in the lidocaine group vs the control group (8.3 min; range: 5.5-12.5; P=0.02). CONCLUSIONS: I.V. lidocaine reduces propofol requirements during the maintenance phase of TIVA, particularly during surgical stimulation. This sparing effect is associated with an increased time to extubation. Owing to its effect on early recovery from anaesthesia, i.v. lidocaine should be taken into account when used as a component of i.v. anaesthesia.

Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children.

BACKGROUND: The performance of eight currently available paediatric propofol pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in healthy children from 3 to 26 months of age. METHODS: Forty-one, ASA I-II children, aged 3-26 months were studied. After the induction of general anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg kg(-1) followed by an infusion of 8 mg kg(-1) h(-1) was given. Arterial blood samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion. Model performance was visually inspected with measured/predicted plots. Median performance error (MDPE) and the median absolute performance error (MDAPE) were calculated to measure bias and accuracy of each model. RESULTS: Performance of the eight models tested differed markedly during the different stages of propofol administration. Most models underestimated propofol concentration 1 min after the bolus dose, suggesting an overestimation of the initial volume of distribution. Six of the eight models tested were within the accepted limits of performance (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed best. CONCLUSIONS: Our results suggest that six of the eight models tested perform well in young children. Since most models overestimate the initial volume of distribution, the use for TCI might result in the administration of larger bolus doses than necessary.

[Laboratory alert value reporting by the clinical laboratory at an academic medical network]. / Aviso de valores de alerta por parte del laboratorio clínico en una red de salud universitaria.

BACKGROUND: An alert value is a result suggesting that the patient is at imminent danger unless appropriate remedial actions begin promptly. Report of alert values (AV) by the clinical laboratories has taken special relevance in recent years due to its contribution to patient's care. AIM: To report results of AV informed during 2007 within the Health Network of the Pontificia Universidad Católica de Chile. MATERIAL AND METHODS: Analysis of AV recorded in a centralized database of the laboratories of the health network, between January and December, 2007. RESULTS: Total number of AV was 5.366, which represented 0.3% of total examinations and corresponded mainly to the clinical chemistry area. Potassium levels generated the higher number of AV detected, followed by positive blood cultures. Eighty two percent of AV corresponded to hospitalized patients. The greater number of AV was reported to intermediate and intensive care services. Thirty two percent of AV was informed to the physician or professional in charge of the patient within 5 minutes of obtaining the results and 79% within 30 minutes. CONCLUSIONS: To obtain a real impact on patient management, it is fundamental to shorten the lapse between the obtainment of tests results and the warning, supported on appropriate computerized systems, and to spread the procedure to all personnel involved in patient's care.

Aviso de valores de alerta por parte del laboratorio clínico en una red de salud universitaria / Laboratory alert value reporting by the clinical laboratory at an academic medical network

Background: An alert value is a result suggesting that the patient is at imminent danger unless appropriate remedial actions begin promptly. Report of alert values (AV) by the clinical laboratories has taken special relevance in recent years due to its contribution to patient's care. Aim: To report results of AV informed during 2007 within the Health Network of the Pontificia Universidad Católica de Chile. Material and methods: Analysis of AV recorded in a centralized database of the laboratories of the health network, between January and December, 2007. Results: Total number of AV was 5.366, which represented 0.3 percent of total examinations and corresponded mainly to the clinical chemistry area. Potassium levels generated the higher number of AV detected, followed by positive blood cultures. Eighty two percent of AV corresponded to hospitalized patients. The greater number of AV was reported to intermediate and intensive care services. Thirty two percent of AV was informed to the physician or professional in charge of the patient within 5 minutes of obtaining the results and 79 percent within 30 minutes. Conclusions: To obtain a real impact on patient management, it is fundamental to shorten the ¡apse between the obtainment of tests results and the warning, supported on appropriate computerized systems, and to spread the procedure to all personnel involved in patient's care (RevMéd Chile 2009; 137: 1137-44).

Immunosuppression with generic tacrolimus and mycophenolate mofetil in renal transplant recipients: preliminary report in Chile.

The association of tacrolimus (TAC) and mycophenolate mofetil (MMF) in renal transplant patients has diminished the incidence of acute rejection. We evaluated the use of generic TAC and MMF as primary immunosuppression in 6 living related (LR) and 11 cadaveric (C) donor renal transplant recipients (9 men, 8 women) of mean age 37 +/- 12 years (range, 17-56 years) between May 2006 and June 2007. From day 0 all patients received TAC, MMF, and prednisone without antibody induction. They were followed for the development of acute rejection, graft loss, side effects, and mortality. Mean follow-up was 7.6 months (range, 2-15 months). No biopsy-proven acute rejection episodes, graft loss, or recipient deaths were observed. Creatinine levels at the end of the study were 1.90 +/- 1.0 mg/dL (range, 0.62-4.25 mg/dL for C recipients and 1.19 +/- 0.15 mg/dL (range, 0.91-1.35 mg/dL) for LR recipients. Mean systolic and diastolic blood pressures were 130/73 mm Hg with 12 patients (70.5%) on antihypertensive therapy with calcium antagonists and beta-blockers. Mean (range) of total cholesterol, triglycerides, and glucose were 172 (110-244) mg/dL, 139 (69-277) mg/dL, and 89 (63-129) mg/dL, respectively. MMF was suspended in 1 patient due to diarrhea and 1 other because of leukopenia. We observed that generic TAC and MMF yielded effective and safe immunosuppression in terms of mortality, biopsy-proven acute rejection, and graft loss with a low incidence of adverse effects during the study period.

Therapeutic drug monitoring of mycophenolic acid in kidney transplant patients: a abbreviated sampling strategy.

Mycophenolic acid (MPA) levels have demonstrated a good correlation with clinical outcomes, but with great pharmacokinetic variability between patients. Therapeutic drug monitoring (TDM) is recommended to include a 12-hour area under the concentration-time curve (AUC). Since full AUC estimates are not practical for routine monitoring, limited sampling strategies have been suggested. We evaluated MPA pharmacokinetics in 18 stable renal transplant patients receiving mycophenolate mofetil (MMF) as part of their immunosuppressive therapy. The correlation between measured and estimated AUC was assessed using 4 different sparse sampling algorithms. The mean values for C(0) and AUC(0-6h) were 1.8 +/- 1.2 mg/L and 31.1 +/- 14.8 mg*h/L, respectively. The dose-corrected AUC(0-6h) was 35.4 +/- 17.9 mg*h/L. Regarding the single time points, C(0) showed a low correlation with AUC(0-6h) (r(2) = .34); C(1.5), the best correlation (r(2) = .72); and C(3), the worst (r(2) = .07). Sparse sample algorithms used to estimate 12-hour AUC including C(0), C(1), C(2), C(3), C(4), and/or C(6) showed a good correlation with the calculated AUC(0-6) (r(2) = .81-.96). The algorithm that used C(0), C(1), C(2), and C(4) showed the best correlation, but we also found a good correlation (r(2) = .91) with C(0), C(1), and C(2). Based on these results, we have suggested using the 3-point algorithm (C(0), C(1), and C(2)) for MPA TDM in stable renal transplant patients due to the good correlation with drug exposure and better functionality than an algorithm using a 4-hour postdose measurement.

Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis.

PCR and FC-ALTA were used to monitor parasite clearance in 54 chronic chagasic patients who had completed therapy with allopurinol (ALLO, n = 31) or itraconazole (ITRA, n = 23) ten years earlier. All patients maintained positive conventional serology. 25 of them showed positive XD (ALLO, n = 11 and ITRA, n = 14) and 29 negative XD (ALLO, n = 20 and ITRA, n = 9). 43 patients were positive by both techniques (ALLO, n = 23 and ITRA, n = 20). Seven of 54 patients were negative by PCR and positive by FC-ALTA and three of 54 were positive by PCR and negative by FC-ALTA. Only one case with both tests negative should be considered cured. Of 29 patients with negative XD, 14 treated ALLO (70 %) and nine with ITRA (77.8 %) showed positive PCR and FC-ALTA. These results do not show differences of efficacy among the drugs, and reinforce the relevance of using sensitive tools such as PCR and FC-ALTA for the follow-up of patients with chronic Chagas disease.

Antígeno prostático complejo: su aporte en el diagnóstico de cáncer prostático / Prostate Specific Antigen: its contribution in the diagnosis of prostatic cancer

El Cáncer de Próstata (CaP) constituye en Chile la tercera causa de muerte por cáncer. El diagnóstico de esta patología en estadíos precoces es determinante en el pronóstico de sobrevida de los pacientes. Actualmente, la forma más frecuente de sospecha de esta enfermedad es a través de la determinación en sangre del Antígeno Prostático Específico (APE). Sin embargo, cada vez con mayor frecuencia, los pacientes presentan elevaciones moderadas de APE (menor de 10 ng/ml), grupo en el que coexisten los pacientes con neoplasias localizadas de mejor pronóstico, con otros que poseen patologías benignas de la glándula. Por esto, es de particular importancia disponer de nuevos métodos, más eficientes en el diagnóstico de estos pacientes. Nuestro objetivo es comparar el rendimiento del Antígeno Prostático Acomplejado (APEc) en la sospecha de CaP, comparándolo con APE y su Fracción Libre (APE L), evaluando si existe una sospecha más eficiente por este método. Corresponde a un estudio retrospectivo que incluye 356 pacientes, que consultan en la semana de la próstata UC entre 1997 y 2002 y que fueron biopsiados por APE mayor o igual a 3,8 ng/ml. Se determinó APE libre y APEc enlos sueros congelados de 347 y 331 pacientes, respectivamente. Se determina sensibilidad (Sen) y especificidad(Esp) en el diagnóstico de CaP y se calculan las curvas ROC para las distintas variedades de APE. Se comparan las áreas de las curvas ROC, considerándose significativo un valor p menor o igual a 0,05. El análisis global muestra que para obtener un 90 porciento de Sen en diagnóstico de CaP, se logra con cortes de APE L:23,9 porciento y APEc: 3,8 ng/ml, correspondiéndoles una Esp de 22,7 y 29 porciento, respectivamente. Las AUC de las tresvariedades de APE para todo el grupo no presenta diferencias (0,69 a 0,73). Entre aquellos pacientes que tienen APE menor a 10 ng/ml (n: 253), con niveles de corte para APE L de 29 porcentaje y APEc de 3,59 ng/ml se logra una Esp de 15p orcentaje y 25,8 porcentaje, respectivamente. En este grupo, la AUC de APE: 0,57 y APEc: 0,65, presentando una diferencia.

Florida's "truth" campaign: a counter-marketing, anti-tobacco media campaign.

The "truth" campaign was created to change youth attitudes about tobacco and to reduce teen tobacco use throughout Florida by using youth-driven advertising, public relations, and advocacy. Results of the campaign include a 92 percent brand awareness rate among teens, a 15 percent rise in teens who agree with key attitudinal statements about smoking, a 19.4 percent decline in smoking among middle school students, and a 8.0 percent decline among high school students. States committed to results-oriented youth anti-tobacco campaigns should look to Florida's "truth" campaign as a model that effectively places youth at the helm of anti-tobacco efforts.