Comparison of multiple definitions for ventilator-associated pneumonia in patients requiring mechanical ventilation for non-pulmonary conditions: preliminary data from PULMIVAP, an Italian multi-centre cohort study.

OBJECTIVES: To compare intensivist-diagnosed ventilator-associated pneumonia (iVAP) with four established definitions, assessing their agreement in detecting new episodes. METHODS: A multi-centric prospective study on pulmonary microbiota was carried out in patients requiring mechanical ventilation (MV). Data collected were used to compare hypothetical VAP onset according to iVAP with the study consensus criteria, the European Centre for Disease Control and Prevention definition, and two versions of the latter adjusted for leukocyte count and fever. RESULTS: In our cohort of 186 adult patients, iVAPs were 36.6% (68/186, 95% confidence interval 30.0-44.0%), with an incidence rate of 4.64/100 patient-MV-days, and median MV-day at diagnosis of 6. Forty-seven percent of patients (87/186) were identified as VAP by at least one criterion, with a median MV-day at diagnosis of 5. Agreement between intensivist judgement (iVAP/no-iVAP) and the criteria was highest for the study consensus criteria (50/87, 57.4%), but still one-third of iVAP were not identified and 9% of patients were identified as VAP contrary to intensivist diagnosis. VAP proportion differed between criteria (25.2-30.1%). CONCLUSIONS: Caution is needed when evaluating studies describing VAP incidence. Pre-agreed criteria and definitions that capture VAP's evolving nature provide greater consistency, but new clinically driven definitions are needed to align surveillance and diagnostic criteria with clinical practice.

Sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin, ceruloplasmin: changes in treatment with two oral contraceptives low in oestrogen.

It is generally assumed that the oral contraceptives cause the carrier proteins to change. Notoriously this effect is used to evaluate indirectly their estrogenicity/gestagenicity ratio. In order to assess the residual intrinsic androgenic activity of two new 19-nor-derivative components, Desogestrel (DG) 150 micrograms and Gestodene (GD) 75 micrograms, both in association with Ethinylestradiol (EE) 30 micrograms, Sex Hormone Binding Globulin, Thyroxine Binding Globulin, Ceruloplasmin and Free Androgen Index (FAI), were studied in 40 young normally cycling healthy volunteers, matched for body mass index and age. The participants were randomly assigned to either EE-DG or EE-GD treatment. A marked significant increase in all the carrier proteins was found. Conversely, the values for FAI decreased significantly. The changes in the two groups were substantially of the same magnitude. These results are an indirect confirmation of the well-known negligible receptor binding affinity of the two progestogen in vitro, also supporting for these compounds the lack of relevant androgenic effects.

PIP: The residual androgenic activity of two new combined oral contraceptives (OCs)--30 mcg of ethinyl estradiol in combination with either 150 mg of desogestrel or 75 mcg of gestodene--was investigated in 40 healthy volunteers. Measured in these volunteers were modifications in transport protein levels. These levels are known to be increased by estrogen, but this increase can be counterbalanced, to varying degrees, by gestagens. For both OCs, there was a marked percentage increase in sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG), thyroxine binding globulin (TBG), and ceruloplasmin (CP) and a similar reduction in total testosterone and the free androgen index. The modifications in SHBG, CBG, TBG, and CP are interpreted as an expression of the correlated value of the estrogenicity/gestagenicity ratio of the OCs studied and suggest that these particular formulations have greater estrogenicity. The relatively negligible biological androgenic activity of desogestrel and gestodene and their elevated affinity progesterone receptor/androgen receptor ratio reflect the high selectivity of these agents. Moreover, the lack of androgenic effects makes desogestrel and gestodene appropriate treatment agents for hyperandrogenism.

Treatment of hirsutism related to micropolycystic ovary syndrome (MPCO) with two low-dose oestrogen oral contraceptives: a comparative randomized evaluation.

In order to evaluate the clinical and endocrinological efficacy of two low-dose oral contraceptives (OC) containing 30 micrograms Ethinylestradiol (EE) and 150 micrograms Desogestrel (DG) and 75 micrograms Gestodene (GD), respectively, an open randomized study was carried out in 34 young hirsute women, matched for body mass index and age. All of them met endocrine and ultrasonic criteria for Micropolycystic Ovary Syndrome (MPCO). The participants were randomly assigned to one of two pill groups (each of 17). The serum values for Total Testosterone (TT), Free Testosterone (FT), Androstenedione (A), Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone Sulphate (DHEAS), 17-Hydroxyprogesterone (17Pg), Sex Hormone Binding Globulin (SHBG), Ceruloplasmin (CP), as well as Ferriman-Gallwey Index (FGI) and Free Androgen Index (FAI) were evaluated prior to and after EE-DG and EE-GD 6 cycle treatment. A significant decrease in TT, FT, A, 17Pg, DHEA, DHEAS, FGI, FAI was observed, SHRG and CP increased significantly. There were no significant differences between the two OC. Our results seem to indicate that both OC are equipotent as far as their pharmacological profile and residual androgenic activity are concerned. Therefore, these OC may represent a highly effective and suitable alternative to the treatment of hyperandrogenism related to MPCO.

PIP: In order to evaluate the clinical and endocrinological efficacy of 2 low-dose oral contraceptives (OCs) containing 30 mcg ethinyl estradiol (EE) and 150 mcg desogestrel (DG) and 75 mcg gestodene (GD) respectively, an open randomized study was carried out on 34 young, hirsute women, matched for body mass index and age. All met endocrine and ultrasonic criteria for micropolycystic ovary syndrome (MPCO); participants were randomly assigned to 1 of 2 pill groups (n=17 each). The serum values for total testosterone (TT), free testosterone (FT), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphase (DHEAS), 17-hydroxyprogesterone (17Pg), sex hormone binding globulin (SHBG), ceruloplasmin (CP), as well as Ferriman-Gallway Index (FGI), and Free Androgen Index (FAI) were evaluated prior to and after EE-DG and EE-GD 6-cycle treatment. Significant decreases in TT, FT, A, 17PG, DHEA, DHEAS, FGI, and FAI were observed; SHBG and CP increased significantly. There were no significant differences between the 2 OCs. These results seem to indicate the both OCs are equally potent in pharmacological profile and residual androgenic activity. Therefore, these OCs may represent a highly effective and suitable alternative to the treatment of hyperandrogenism related to MPCO.

Effectiveness of short term canrenone treatment in idiopathic hirsutism.

In order to verify the anti-androgenic effects of canrenone, the major metabolite of spironolactone, 9 normally cycling women with post-puberal hirsutism, were orally administered the drug (200 mg per day for three months). In all patients, the clinical score, according to the method of Ferriman and Gallwey (F.G.I.: Ferriman-Gallwey Index), as well as endocrine function tests, including total and free testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, 17-OH-progesterone, basal and ACTH stimulated cortisol, were evaluated prior to and after canrenone treatment. A significant reduction in hair growth (F.G.I. = 18 +/- 2 vs 23 +/- 3, p less than 0.001), and also a significant decrease, with regard to endocrine parameters, of total testosterone (0.5 +/- 0.1 vs 0.9 +/- 0.3 p less than 0.01), free testosterone (2.7 +/- 0.7 vs 4.7 +/- 1.7, p less than 0.005), dehydroepiandrosterone sulphate (228 +/- 38 vs 314 +/- 81, p less than 0.02), and sex hormone binding globulin (62.5% of basal values, p less than 0.001), were observed. Serum levels of 17-OH-progesterone, and basal and ACTH stimulated cortisol were not significantly different from pretreatment values. It is concluded that the biochemical and clinical parameter improvement, along with a well-preserved cortisol secretion (unchanged levels of 17-OH-progesterone), suggest that canrenone may represent an effective therapy for idiopathic post-puberal hirsutism.