A model for integrated home care of frail older patients: the Silver Network project. SILVERNET-HC Study Group.

Home care programs for the treatment of frail elderly have been developed in many countries around the world. In the Silver Network project all services are provided in an integrated fashion by one "single entry" center, differently from the traditional fee-for-service or not integrated systems. The delivery of health and social services for frail elderly individuals are integrated and coordinated by a case manager who uses a "second generation" assessment instrument, the Minimum Data Set for Home Care (MDS-HC). We describe the principal clinical and functional characteristics of nearly 1300 patients admitted between 1997 and 1998 to such an integrated home care program in eleven Italian Health Agencies. The database, derived from the serial MDS-HC assessments of each patient, provides a unique opportunity to delineate the different criteria for eligibility for home care, and compare the selected populations of the participating Health Agencies.

Effect of piroxicam therapy on granulocyte function and granulocyte elastase concentration in peripheral blood and synovial fluid of rheumatoid arthritis patients.

The effect of piroxicam therapy (20 mg/day for 15 days) on various polymorphonuclear granulocyte (PMN) responses and on PMN elastase concentration was investigated in nine patients with active rheumatoid arthritis. Peripheral blood and synovial fluid samples were collected before starting therapy and 12 h after the last dose of the drug. All patients were evaluable for peripheral blood analysis and six for synovial fluid analysis. Piroxicam therapy had no effect on PMN random migration and phagocytosis, while it significantly reduced both FMLP-induced aggregation and FMLP-induced chemotaxis. This seems mainly due to an effect on FMLP binding, as no differences were observed after therapy in PMA- and PHA-induced aggregation as well as in serum-induced chemotaxis. In contrast, a marked impairment of NBT test and PMA- and FMLP-induced superoxide anion (O2-) production was found after piroxicam therapy. This effect was as evident in peripheral blood as in synovial fluid PMN. Also, a significant reduction in synovial fluid PMN number and synovial fluid PMN elastase concentration (elastase-alpha 1-proteinase complex) was found after treatment. It is concluded that piroxicam may act at different sites on various PMN responses. Its effect on O2- generation and PMN elastase concentration in synovial fluid may have an important role in reducing destruction of arthritic joint tissue.

[Multicenter research on cefoperazone efficacy and tolerance in the therapy of urinary and respiratory infections]. / Indagine multicentrica sull'efficacia e sulla tollerabilità del cefoperazone nella terapia delle infezioni urinarie e respiratorie.

In this multicenter study the authors evaluated the clinical and microbiological efficacy and the local and general safety of cefoperazone sodium in 1,546 patients (946 males and 600 females, mean age 61.3 years) with lower respiratory tract (1,044) and urinary tract (539) infections. Results were very encouraging with 95.3% of clinical cures or improvement, 91.6% of microbiological eradication, and a local and general safety which was always extremely high, i.e. 96.9% and 98.3% respectively.

Sulbactam/ampicillin versus cefotetan in the treatment of obstetric and gynecologic infections.

In an open, randomized clinical study, the safety and efficacy of sulbactam/ampicillin was compared to that of cefotetan in 95 hospital patients with gynecologic or obstetric infections. Sulbactam/ampicillin (1 g:2 g), was administered intravenously every 8 h to 46 patients, and cefotetan (2 g) was administered intravenously every 12 h to 49 patients. All 23 patients with obstetric infections and 18 of the 23 patients with gynecologic infections treated with sulbactam/ampicillin were evaluated as cured. All 21 patients with obstetric infections and 23 of the 28 patients with gynecologic infections treated with cefotetan were evaluated as cured. No side effects requiring discontinuation of therapy or reduction of the dose administered, were observed.

The treatment of onychomycosis with a new form of tioconazole.

The difficulties encountered in the treatment of onychomycosis are primarily related to the necessity of prolonged systemic therapy. Many of these difficulties could, then, be avoided by the use of an effective local treatment. The present study compared the effectiveness and tolerability of two topical ungual preparations: a 28% solution of tioconazole and a 2% tincture of miconazole. The therapeutic results and tolerability of both preparations were found to be satisfactory. The tioconazole preparation proved to be slightly more effective although the difference was not statistically significant.

Pharmacokinetics of bacampicillin using a compartment model with zero-order absorption.

The pharmacokinetics of bacampicillin, a prodrug of ampicillin which is absorbed from the gastrointestinal tract, were studied in 10 healthy male volunteers after administration of 1,200 mg in a single oral dose. The pharmacokinetic analysis was carried out by applying a single-compartment kinetic model with zero-order absorption. The apparent duration of absorption (T) was about 1 h for all subjects. The peak plasma concentrations (Cmax) were 17.89 +/- 1.82 micrograms/ml, and the mean plasma half-life during beta-phase was 1.17 +/- 0.14 h. The area under the curve was 41.22 +/- 5.29 micrograms.h/ml. The mean urinary recovery during 24 h amounted to 76.4 +/- 3.65% of the dose.

Microbiological properties of sulbactam combined with ampicillin.

Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin). The intrinsic activity of Sbt/Amp was satisfactory and comparable to that of other beta-lactams and no significant difference was observed against beta-lactamase producing or non-producing bacteria. Besides, it was determined that sulbactam, when combined with ampicillin at different ratios (1:2, 5:1), with and without preincubation (60 min) reduces the hydrolysis of ampicillin determined by ten different standard beta-lactamases. The hydrolysis rates of ampicillin become as low as those of cefoxitin, cefamandole and ceftriaxone, which are beta-lactamase stable cephalosporins. In fact, all the antibiotics under examination were slightly hydrolyzed by several beta-lactamases, but such slight hydrolysis did not affect the antibacterial activity against beta-lactamase producing bacteria. About 50% of non-beta-lactamase producing bacteria (18 strains of different bacterial species) produced an inducible beta-lactamase after ten daily subcultures with sub-inhibitory concentrations of each antibiotic, but minimum inhibitory concentrations (MICs) of Sbt/Amp never increased after stimulation in contrast with other drugs whose MICs were much higher in consequence of this procedure. Finally, no spontaneous resistant mutant to Sbt/Amp was detected, but several mutants appeared in response to the other drugs. Sulbactam makes ampicillin as effective as beta-lactamase stable cephalosporins and its use does not determine an increase of resistance or selection of resistant mutants.

Clinical efficacy and safety of sulbactam/ampicillin in patients suffering from chronic liver disease.

Sulbactam is a new beta-lactamase inhibitor with pharmacokinetic characteristics in humans similar to those of ampicillin. A total of 41 patients hospitalized in the Clinic of Infectious Diseases, University of Naples, for chronic liver diseases, were treated with sulbactam/ampicillin (ratio 1:2) for urinary, respiratory, biliary tract or soft tissue infections. Sulbactam/ampicillin was administered im or iv at a dosage of 3-9 g/day depending on the site and severity of the infection. All the patients treated with sulbactam/ampicillin had clinical signs and symptoms of infection, and all the organisms isolated were sensitive to sulbactam/ampicillin (MIC less than 16 mg/l). For both Gram-positive and Gram-negative bacteria the sulbactam/ampicillin MICs were much lower than the ampicillin MICs. In agreement with the favourable in-vitro results, we observed good therapeutic efficacy. 85% of the patients recovered or improved within a few days of therapy, with no clinical relapses, and in 81% of the infections the responsible bacteria were completely eradicated. We observed a low number of side effects (3/41 oral candidosis; 3/41 pain at the im injection site) and no change in the blood chemistry tests.

Pharmacokinetics of cefoperazone after single and multiple doses.

The pharmacokinetics of cefoperazone was determined following single and multiple intravenous and intramuscular administrations in man. Ten subjects at each dose level were given eleven successive doses, at 12 h intervals of 500 and 1000 mg i.m. and i.v.. Serum concentrations and urinary excretion were determined in all subjects after the first, fifth and eleventh doses. The first i.m. doses yielded mean peak serum levels of 37 micrograms/ml and 76 micrograms/ml at 1.0 h after injection. The first i.v. doses yielded mean serum levels of 93 and 180 micrograms/ml at 5 min after the injection. No tendency toward drug accumulation was observed on multiple dosage. The pharmacokinetics could be described by a linear, open, two-compartment model of drug distribution. The terminal serum half-life (2.1-2.4 h after i.v. doses and 2.6-2.8 h after i.m. doses) remained essentially constant over the period of the study by dose levels. The no-significant differences of areas under the curve between the two routes, at two doses, show the absolute bioavailability of cefoperazone was about 95% following i.m. administration. The high binding to serum proteins (90%) influences favourably the pharmacokinetic parameters of cefoperazone. It yielded high and prolonged serum concentrations and has very useful distribution properties. These favourable properties, together with its good antibacterial activity, suggest that cefoperazone will be effective in treating bacterial infections in human beings.

Endocrine study of anorexia nervosa.

The main objective of the study was to evaluate the endocrinological picture of anorexia. The sample consisted of 23 anorectic patients (20 females, 3 males) with a control group of 10 normal females and 5 normal males. All participants underwent a work-up which included testing for hypothalamic, hypophyseal, thyroidal, adrenal, gonadal functioning and glucose metabolism. Our results revealed a reduced urinary output and low serum levels of gonadotropins with different responses to LHRH correlating with the stage of the illness. We found reduced urinary estrogens and elevated testosterone levels in females. Males demonstrated a reduction of testosterone. While basal prolactinemia was normal in both sexes, males showed an exaggerated response to TRH. The thyroid function study in anorectic patients revealed a decrease in T3 and in free T3 and an increase in reverse T3. Free T4 was slightly increased with normal T4 levels. Basal TSH was normal with a delayed peak after TRH. We also noticed in the anorectic population reduced basal glucose levels with a flat glucose curve; reduced insulin levels with a slight increase after glucose administration; elevated basal GH with a fair response to L-Dopa; elevated serum cortisol with loss of circadian rhythm and slightly inhibited by dexamethasone. In addition, both noradrenalin and VMA were reduced. We concluded that the multiple endocrine abnormalities found are consistent with hypothalamic dysfunction. The etiology of this dysfunction remains for the endocrinologist highly controversial.

Thyroid function in altered nutritional state.

We studied plasma concentrations of TSH (basal and after TRH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), free T4 and free T3 in thirty obese subjects, twenty patients with anorexia nervosa, fifteen malnourished subjects and twenty normal weight subjects. Total serum T4 values were similar for the four groups of subjects while serum free T4 values were slightly increased in anorexia nervosa and normal in the other groups. Serum total and free T3 levels were both significantly decreased in anorexia nervosa and malnutrition, and within normal limits in obesity. The mean serum rT3 level was increased in anorexia nervosa and malnutrition while was reduced in obesity. A delay in peak response of TSH to TRH stimulation (30' rather than 20') was noted in anorexia and malnourished patients. The results suggest that these alterations of serum iodothyronines are due to a different peripheral conversion of T4 to T3 according to nutritional status.