Universal vaccination of children against hepatitis A in Chile: a cost-effectiveness study.

OBJECTIVE: To evaluate the healthcare and economic impact of routine hepatitis A vaccination of toddlers in Chile. METHODS: We used a dynamic model of hepatitis A infection to evaluate the impact of a two-dose vaccination program, administered at ages 12 and 18 months. The model incorporated the changing epidemiology of hepatitis A in Chile and the development of vaccine-induced herd immunity. Our analysis was conducted from the public payer perspective, and an estimation of the societal perspective was performed. Costs are expressed in 2005 U.S. dollars. RESULTS: Vaccination of toddlers rapidly reduced the healthcare burden of hepatitis A. In the base case (95% vaccination coverage, 100-year time horizon, 1% annual decrease in force of infection), the average number of infections fell by 76.6% annually, and associated deaths fell by 59.7%. Even at 50% coverage, the program reduced infection rates substantially. Routine vaccination of toddlers had economic as well as health benefits, saving $4,984 per life-year gained (base case scenario). The program became cost saving after 6 years, and its overall cost-effectiveness per life-year gained was largely unaffected by changes in disease-related costs, herd immunity, coverage rate, and annual decrease in force of infection. CONCLUSIONS: Routine vaccination of toddlers will reduce the rates of symptomatic hepatitis A and associated mortality. The two-dose schedule evaluated here will be less expensive than disease-related costs in the absence of vaccination from the sixth year of its implementation. These findings support the establishment of a routine vaccination program for toddlers in Chile.     

Mespirenone and other 15,16-methylene-17-spirolactones, a new type of steroidal aldosterone antagonists

The ability of a series of 15,16-methylene-spirolactones in comparison to known antimineralocorticoids to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The standard procedure involved continuous i.v. infusion with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 micrograms/(kg X h)] resulting in a long-lasting reduction of renal sodium excretion, increase of renal potassium excretion and hence decrease of the urinary Na/K-ratio. In some experiments sodium input was increased (0.2% NaCl + 4.3% glucose or 0.9% NaCl, respectively). The test drugs either were administered orally 1 h before start of the infusion or were added to the infused solution. With the exception of two steroids which could only be tested at single doses, all compounds were administered at three doses ranging from 2.2 to 40 mg/kg (p.o.) or from 0.83 to 6.7 mg/kg/h (i.v.). Spironolactone or spirorenone (oral administration) and potassium canrenoate (i.v. infusion) served as reference compounds. The antimineralocorticoid activity of the steroids was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used as controls. To obtain preliminary information on potential antiandrogenic and progestogenic (side-)effects, binding of the test-compounds to androgen receptors (rat prostate cytosol) and progestogen receptors (rabbit uterus cytosol) was measured in vitro using 3H-dihydrotestosterone (DHT) and 3H-progesterone (prog.) as tracer and unlabelled DHT and prog. as references. All steroids tested exhibited antimineralocorticoid activity. For compounds tested at three doses levels the potency relative to the standard used was evaluated using regression analysis based on the Na/K-ratio or the log (Na X 100)/K-ratio. The relative potency of the other compounds was estimated by comparing the biological effect of single doses of test drug and standard drug, respectively, using nonparametric statistical tests.(ABSTRACT TRUNCATED AT 400 WORDS)     

Indirect, noninvasive evaluation of pressure wave transmission in essential hypertension

Blood pressure, carotid-femoral and brachioradial pulse wave velocities were measured in 123 male subjects: 32 normal subjects and 91 age-matched patients with sustained essential hypertension. The ratio between brachioradial (BR) and carotid-femoral (CF) pulse wave velocities was used as a marker of pressure wave amplitude changes from the aorta to the brachial artery. The ratio was similar in normotensive and hypertensive subjects and decreased with age to the same extent in both populations. In older subjects, the decrease in the ratio indicated that the amplitude of pulse pressure was quite similar in the aorta and the brachial artery whether the subjects were normotensives or hypertensives. The study provided evidence that adaptive changes occur in the arterial (aortic) wall in hypertension, for the effects of age on pressure wave transmission are similar in normal subjects and hypertensive patients. Such findings may be of prime importance in understanding the brachial blood pressure readings of patients with hypertension.     

Pain and morbidity of an extensive prostate 10-biopsy protocol: a prospective study in 289 patients.

PURPOSE: Some studies imply that increasing the number of prostate biopsy cores may improve the cancer detection rate. We performed a prospective study to evaluate pain and morbidity after an extensive transrectal ultrasound guided 10-core biopsy protocol. MATERIALS AND METHODS: A total of 289 consecutive men with abnormal digital rectal examination findings and/or increased prostate specific antigen underwent extensive prostate biopsy involving 6 sextant and 4 peripheral biopsies. Each received an information leaflet a few days before the procedure. A single dose of fluoroquinolone and a rectal enema were administered before biopsy. In no case was the procedure performed using anesthesia. Immediately after biopsy patients were asked to complete a self-administered nonvalidated questionnaire evaluating the degree of pain and/or discomfort using a visual analog scale. In another questionnaire they listed the side effects noticed during month 1 after biopsy. RESULTS: Although 48% of the 275 men who completed the initial questionnaire reported anxiety before the procedure, 78.8% of them were completely reassured by the information brochure. Of the 275 patients 47.6% described the procedure as painful, including only slightly painful (analog visual scale 3 or less) in 67.9%, while 33.8% described it as uncomfortable but not painful and 18.6% thought that it was neither painful nor uncomfortable. Of the 115 patients who engaged in sexual intercourse during month 1 after the procedure 78.3% noticed hematospermia an average of 10.9 days in duration. Of the 164 men who completed questionnaire 2, 74.4% noticed hematuria an average of 2.7 days in duration, 3.7% noticed pyrexia and 1.2% noticed acute prostatitis. In the 59 patients (36%) who reported delayed perineal pain it was slight in 64.4%, moderate in 30.5% and severe in 5.1%. No patient required hospitalization. CONCLUSIONS: Although minor complications are common, the extensive 10-core prostate biopsy protocol is associated with few major complications. The occurrence and intensity of pain and discomfort are in the range reported after the standard 6-core biopsy protocol.     

In vitro action of fosfomycin combined with rifampicin, pefloxacin and imipenem on staphylococci (checkerboard method in a liquid medium)

The combined activity of fosfomycin with rifampin, pefloxacin and imipenem was investigated, by the checkerboard method performed in liquid medium, against 50 clinical isolates of staphylococci (25 Staphylococcus aureus and 25 coagulase-negative staphylococci). The combination of fosfomycin plus rifampin had an additive bacteriostatic effect and an antagonistic bactericidal effect. Fosfomycin combined with pefloxacin was found to be additive or moderately synergistic. Fosfomycin in combination with imipenem was generally highly synergistic, especially against meticillin-resistant strains; however the bactericidal effect was occasionally antagonistic.     

Combined heart and kidney transplantation using the same donor

A 45-year-old man received a combined heart and kidney transplant provided by the same donor. The patient was in the terminal stage of renal failure and was submitted to 3 sessions of haemodialysis per week for 2 years before transplantation. A dilated cardiomyopathy with severe impairment of left ventricular (LV) function was discovered, precluding renal transplantation alone. In the postoperative course, a cardiac rejection episode was detected by echocardiography and documented by endomyocardial biopsy; no simultaneous rejection of the kidney could be detected. The patient was discharged after 2 months, and he resumed a normal and active life. The specific problems raised by the management of such multi-organ transplantation are briefly reviewed.     

Enhancement of ricin A chain immunotoxin activity by perhexiline on established and fresh leukemic cells

In the perspective of increasing the clinical potential of ricin A chain immunotoxins (RTA-ITs), perhexiline (Pex) and four structural analogues (Pex 2, Pex 3, Pex 7, and Pex 11) were evaluated for their ability to enhance RTA-IT activity in vitro. Only perhexiline significantly enhanced the cytotoxic activity of anti-CD5 RTA-ITs, T101 and T101-F(ab')2, on CEM III cell line (30- to 2000-fold), and of anti-HLA-DR RTA-IT, HNC-241, on both RAJI cell line (greater than 100-fold) and two immortalized cell lines originating from patients suffering from B-cell chronic lymphocytic leukemia, EHEB and FS2 D5 (10-fold). On 16 consecutive fresh B-cell chronic lymphocytic leukemia cell samples, significant T101-F(ab')2 RTA-IT and HNC-241 RTA-IT enhancement was observed with perhexiline which was comparable to that of NH4Cl and monensin. Perhexiline almost completely blocked RTA-IT intracellular degradation and profoundly modified its routing. These observations were linked to perhexiline-induced lipidosis via inhibition of sphingomyelinase activity. In conclusion, since the concentrations used are relevant with the pharmacokinetics of this agent, perhexiline appears to be a promising agent for in vivo enhancement of ricin A chain immunotoxins.