Cost-effectiveness of pneumococcal vaccination of older people: a study in 5 western European countries.

Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged > or =65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from approximately 11,000 to approximately 33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged > or =65 years.

Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity.

Corticosteroid-binding globulin (CBG) is the plasma transport protein that regulates the access of glucocorticoid hormones to target cells. Genetic deficiencies of CBG are rare, and only a single human CBG variant (Trancortin Leuven) has been related so far to decreased cortisol-binding affinity. We report here on a 43-yr-old woman, referred for chronic asthenia and hypotension, with repeatedly low morning serum cortisol levels (22-61 nmol/L; normal range, 204-546 nmol/L), normal plasma ACTH levels (38-49 pg/mL; normal, <50 pg/mL), and normal urinary cortisol (10-76 nmol/24 h; normal range, 10-105 nmol/24 h). An increased percent-free (dialysable fraction) serum cortisol (8.7-9.7%, normal range, 2.9-3.9%) suggested abnormal CBG binding activity. Indeed, she had a low serum CBG concentration (24 mg/L vs. 44+/-6 mg/L in normal women), and the affinity of her CBG for cortisol was decreased (association constant, Ka = 0.12 L/nmol vs. 0.82+/-0.29 L/nmol). In her immediate family members, the serum CBG concentration and cortisol-binding activity were normal in her husband, but the four living children had slightly lower serum CBG concentrations than the reference ranges for their pre- and postpubertal status. Measurements of cortisol distribution in undiluted serum indicated that an increase in the percentage of nonprotein-bound cortisol offsets the low cortisol levels to give approximately normal concentrations of free cortisol in serum. Direct sequencing of PCR-amplified exons encoding CBG revealed that the proband was homozygous for a polymorphism (GAC-AAC) in the codon for residue 367, which results in a Asp367-->Asn substitution. Her children were heterozygous for this polymorphism. When this nucleotide change was introduced into a normal human CBG complementary DNA, for expression in Chinese hamster ovary cells, Scatchard analysis demonstrated that the Asn367 substitution reduced the affinity of human CBG for cortisol by approximately 4-fold (Ka = 0.15 L/nmol), as compared to normal recombinant CBG (Ka = 0.66 L/nmol). These results suggest that Asp367 is an important determinant of CBG steroid-binding activity and that normal negative regulation of the hypothalamic-pituitary-adrenal axis is maintained by relatively normal serum-free cortisol concentrations, despite a marked reduction in the steroid-binding affinity of this novel human CBG variant, which we have designated as CBG-Lyon.

Postmenopause hormone treatment in women with NIDDM or impaired glucose tolerance: the MEDIA randomized clinical trial.

OBJECTIVE: To assess the biological safety of four hormone replacement treatment (HRT) combinations in women with non insulin dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT). SUBJECTS AND METHODS: Randomized, double-blind, placebo-controlled trial to analyze the variation of fibrinogen, factor VII, PAI1, and TG blood levels in women (n=99), with NIDDM or IGT, receiving a 3-month course of either oral oestradiol (1 or 2 mg) combined with Chlormadinone Acetate 5 mg, or transdermal oestradiol 50 microg/24 h in association with Norethisterone Acetate (11.2 or 22.4 mg), or placebo. Follow-up lasted 3 months. RESULTS: Ninety nine patients, mean age 56 years (SD 5), mean diabetes duration 7 years (S.D. 7), mean glycated hemoglobin (7.3%) were enrolled. There was no significant difference between the groups for any of the primary hemostasis criteria (n=77). Triglycerides (TG) variation significantly differed between groups, P=0.01, from -21% in the large patch group, to +22% in the placebo group (n=82). Treatment administration routes did not significantly differ for any of the criteria. There was a significant difference in the total cholesterol variation between groups, from +8.7% in the placebo group to -10.8% in the oral 1 mg group (P=0.001). CONCLUSION: The treatments had no highly deleterious effect in these patients with NIDDM or with IGT. Long-term trials can be performed with such patients, and an hormone treatment can be prescribed to relieve symptoms. Since these patients had a well-controlled NIDDM, results might be different in less well-controlled diabetes. The data do not support the hypothesis of an impaired oestrogen effect in patients with NIDDM.

[The unexpected occurrence of spontaneous pregnancy during hormone replacement therapy for premature menopause]. / Survenue d'une grossesse spontanée sous traitement substitutif hormonal pour ménopause précoce.

Ovarian failure may be an irreversible consequence of cancer treatment for premenopausal woman. The diagnosis must be do of repeated gonadotropins and estrogen levels. A case of pregnancy is reported in a 26-year-old woman with iatrogenic menopause since eleven years and receiving estrogen/progesterone replacement therapy. The patient's age at the time of therapy, the amount of radiation that the ovaries received and the dose of the antineoplastic agent(s) are the critical factors for determine future ovarian functioning.