Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of a multicenter, double-blind trial

BACKGROUND: Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias. OBJECTIVE: This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia. METHODS: This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination. RESULTS: Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results. CONCLUSION: The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.     

Long-term treatment with metformin in type 2 diabetes and methylmalonic acid: Post hoc analysis of a randomized controlled 4.3 year trial

Aims

Metformin treatment is associated with a decrease of serum vitamin B12, but whether this reflects tissue B12 deficiency is controversial. We studied the effects of metformin on serum levels of methylmalonic acid (MMA), a biomarker for tissue B12 deficiency, and on onset or progression of neuropathy.

An open study with acamprosate in Belgium and Luxemburg: results on sociodemographics, supportive treatment and outcome

This open study on 614 alcohol-dependent patients from 51 centres in Belgium over 24 weeks collected data on the sociodemographic, medical and drug safety profiles and the type of psychosocial support most commonly associated with acamprosate. Psychiatric problems (34%) and gastro-intestinal ulcers (15%) were the most frequent other medical diagnoses. As supportive treatment, 48% of patients received individual psychotherapy, 25% group therapy, 16% relapse prevention and coping skills, 9% brief intervention and 2% family therapy. Fifteen (29%) centres used only 1 form of supportive treatment, 14 (27%) used 2 forms of support, 16 (31%) used 3 forms, 4 (8%) used 4 and only 2 centres (4%) used all 5 supportive treatment options. Three hundred and fifty-nine patients dropped out of the study. At any moment during the treatment period, up to 11% relapsed, 9% had binge drinking and 9% had drinking lapses. The quantity of alcohol consumption during relapse, lapse or binge drinking showed a considerable drop in the mean number of drinks per day, from 19.53 before treatment to 4.23-7.83 drinks for lapse drinking, 9.27-14.62 drinks for binge drinking and 4.96-10.29 drinks per day for relapse. All 8 dimensions of the SF36 quality of life questionnaire improved over the treatment period. Acamprosate was well tolerated by all patients.     

Combined Efficacy of Acamprosate and Disulfiram in the Treatment of Alcoholism: A Controlled Study

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 380 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using χ², t , and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients ( p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 ( p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group ( p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.     

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles

Research questionCan previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?DesignRetrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.ResultsIn addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log²(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.ConclusionsEvidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.     

Short scale to measure female sexuality: adapted from McCoy Female Sexuality Questionnaire.

This article examines sex-questionnaire data using the Personal Experiences Questionnaire (PEQ; Dennerstein, Hopper, & Burger, 1997). We used data from a population-based sample of 354 Australian mid-aged women and an optimization procedure in order to reduce the length of the PEQ while retaining items measuring the components of female sexual functioning and key determinants. Eight items were selected. We recommend retaining the item related to orgasm (rejected for parsimony only). Eight of the nine items were from the McCoy Female Sexuality Questionnaire, confirming the validity of this source scale. The original wording in the McCoy scale is recommended as considerable data has now become available on reliability and validity.     

Naftidrofuryl can enhance the quality of life in patients with intermittent claudication.

BACKGROUND: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. PATIENTS AND METHODS: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values. RESULTS: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.     

Association between hormonal changes at menopause and the risk of a coronary event: a longitudinal study

OBJECTIVE: To investigate the association of hormone levels at menopause, lifestyle variables, and body composition with the predicted 10-year risk of a coronary event, calculated using the PROCAM scoring system, in a population-based sample of Australian-born, middle-aged women. DESIGN: A 9-year prospective study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews, fasting blood, and physical measurements were taken annually. The risk of an acute coronary event was calculated using the PROCAM scoring system (includes: age, low-density lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides). RESULTS: Retention rate after 8 years of follow-up was 88% (n = 387). In women not using hormone therapy (HT): higher than average body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than average estradiol levels (P < 0.005), estradiol levels that decreased (P < 0.001), and high free testosterone levels (P < 0.05) were associated with increased risk of a coronary event. There was a trend for high exercise frequency to be associated with a decreased risk (P < 0.07). After BMI and lifestyle variables were taken into account, use of HT did not have a significant effect on risk of a coronary event. CONCLUSION: In this longitudinal observational study of middle-aged Australian-born women, high BMI, an increase in BMI, high free testosterone, low estradiol, and a decrease in estradiol levels were the main determinants of increased risk of an acute coronary event, based on the PROCAM scoring system calculation. More frequent exercise tended to lower the risk.     

Hysterectomy in six European countries

Gynaecologists have been criticized in recent years because of their attitude towards hysterectomy; it is often stated that they are too ready to consider hysterectomy to be indicated and that hysterectomies are carried out too frequently.In order to obtain insight into the incidence of hysterectomy, 2066 women between 40 and 70 yr of age, composing a sample covering 6 European countries, were asked whether they had undergone this operation. Of the total sample, 11.4% had been hysterectomized, the highest percentage being found in Italy (15.5%) and the lowest in France (8.5%).The most important factor that influenced the relative frequency of hysterectomy was age: the percentage of women who had undergone hysterectomy increased with age up to 55–59 yr, but fell thereafter. Another significant factor was civil status; there were fewer divorcees or widows at the moment of operation than married or never-married women.The relationship between the incidence of hysterectomy and age is a parabolic one. To explain this curve the authors postulate that two trends must have played a rôle: firstly; a greater need for hysterectomy with increasing age and, secondly a decrease in the reluctance of the gynaecological profession to perform a hysterectomy and/or of women to undergo this operation.Statistical analysis confirms the existence of this second trend over the period 1960–1975. The chances of a young woman losing her uterus before her 70th year went up linearly to 19.8% in 1975. By extrapolation a figure of 21% is obtained for 1980. Satisfaction with the result of the operation was lowest in Italy and Germany; satisfaction was also lowest in rural areas.