What are Probable Olfactory Markers of Alcohol Dependence?

As the olfactory system is closely connected with the brain areas responsible for the most crucial alterations in psychiatric populations, especially cognitive and emotional impairments, the study of olfactory processing may be a relevant approach to identify specific markers of alcohol dependence. The aim of this study was to propose the probable olfactory markers for alcohol dependence through a study of the olfactory parameters that involve the central olfactory pathway. We recruited the same 41 alcohol-dependent patients in an early (day 8) and late (day 67) stage of abstinence and 41 controls matched for gender, age, and smoking status. The participants underwent clinical assessments and several olfactory evaluations. The results revealed on one hand, the persistence of decreased intensity of positive emotion (happy), increased intensity of negative emotion (sad), and increased citation of surprise in patients, suggesting the presence of probable trait markers of alcohol dependence. On the other hand, we found decreased hedonic score for pleasant and neutral odorants, and decreased odor familiarity judgment only in the early stage of evaluation as probable state markers for alcohol dependence. These results may be underpinned by several neuropsychological alterations specific to this disease and their evolution after weaning. Further studies are needed to replicate these findings and to confirm the specificity and sensitivity of the olfactory tests in a larger sample of patients. The olfactory perception of all controls must be also retested in order to determine the specific state and/or trait markers of alcohol dependence.

Comparing raloxifene with continuous combined estrogen-progestin therapy in postmenopausal women: Review of Euralox 1.

OBJECTIVES: To review the main findings of the Euralox 1 study - a multicentre, randomised, double-blind study conducted in 1008 healthy postmenopausal women allocated to raloxifene (n = 495) or continuous combined estrogen-progestin therapy (ccEPT; n = 513) for 6 months -- and provide an overview of the risks and benefits of raloxifene and ccEPT. METHODS: A review is provided of previously published findings on uterine safety (bleeding rates and changes in endometrial thickness and uterine volume), gynaecological adjudication, cardiovascular risk (lipids, fibrinogen), adverse events, compliance, treatment satisfaction and quality of life. New data on biochemical markers of bone turnover (serum N-telopeptides and C-terminal telopeptides of type I collagen; NTX and CTX) assessed before and after 6 months' treatment are presented. RESULTS: Raloxifene caused less uterine bleeding than ccEPT and, unlike ccEPT, did not alter endometrial thickness or uterine volume. Serum CTX and NTX levels were reduced in both treatment groups, but the reduction was significantly greater with ccEPT. The two treatments had differential effects on lipids and fibrinogen levels; raloxifene had more favourable effects on serum HDL, the LDL/HDL ratio, and plasma fibrinogen. Raloxifene was associated with fewer adverse events or discontinuations, and this was associated with higher treatment satisfaction and better self-reported compliance. CONCLUSIONS: The clinical risk-benefit profile of raloxifene derived from the intermediate endpoints of this study suggests that it may be a better alternative to ccEPT for preventing long-term postmenopausal health risks in healthy postmenopausal women who are not suffering from vasomotor symptoms.

Uterine effects of estrogen plus progestin therapy and raloxifene: adjudicated results from the EURALOX study.

OBJECTIVE: To compare the incident rate of abnormal endometrial findings in postmenopausal women receiving treatment with either 60 mg of raloxifene or a continuous combined estrogen plus progestin therapy containing 2 mg of 17 beta-estradiol plus 1 mg of norethisterone acetate for a duration of up to 12 months. METHODS: One thousand eight asymptomatic postmenopausal women with osteoporosis or cardiovascular risk factors with an endometrial thickness of less than 5 mm at baseline participated in this prospective, randomized, double-blind trial that lasted 6 months; 347 of these women also participated in a 6-month extension. Women with repeated bleeding or an increase in endometrial thickness to above 5 mm were subjected to saline-infused sonohysterography or hysteroscopy with biopsy. Sonographic, histologic, and clinical findings were adjudicated by a panel of 4 experts blinded with respect to patients' treatments. All adjudicated patients were grouped into 15 diagnostic categories according to predefined criteria. RESULTS: Three hundred thirty-four women needed adjudication during the core phase, 73 (14.7%) of those taking raloxifene and 261 (50.9%) taking continuous combined estrogen plus progestin therapy (P <.001). Compared with raloxifene, women using continuous combined estrogen plus progestin therapy had significantly higher rates of benign endometrial proliferation (8.8 versus 1.2%, P <.001), endometrial polyps (4.3 versus 2.0%, P =.048), and cystic atrophy (5.5 versus 1.2%, P <.001). CONCLUSION: Women using continuous combined estrogen plus progestin therapy more often have benign endometrial pathology and, in our study, more often required the protocol-specific gynecological follow-up assessments for safety reasons, as compared with those using raloxifene. These findings are of clinical relevance when choosing the most appropriate therapy for postmenopausal health risks such as osteoporosis.