Biomedical subjects

Philippe Lehert

Publications and source records attributed to Philippe Lehert.

At least 19 recordsLinked to original sources

PubMed2006

Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation.

This is the first US study to evaluate the clinical efficacy of acamprosate (Campral), a newly FDA-approved medication for maintaining abstinence in patients with alcohol dependence following alcohol withdrawal. We compared effects of the standard 2 g dose (n=258) and an exploratory 3 g dose of acamprosate (n=83) versus placebo (n=260), and evaluated drug safety in a double-blind, placebo-controlled 6-month trial conducted in 21 outpatient clinics across the US. Participants were 601 volunteers with current alcohol dependence recruited primarily by advertisement. All patients concomitantly received eight sessions of brief manual-guided counseling (www.alcoholfree.info). The main outcome measure was the percentage of alcohol-free days over the 6-month study. Self-report was validated by breath alcohol concentration, gamma-glutamyltransferase (GGT) and collateral informant interviews. The percentage of abstinent days did not differ significantly across groups in a priori analysis (54.3% for placebo, 56.1% for 2 g, 60.7% for 3 g). Post-hoc analysis controlling for baseline variables and treatment exposure found acamprosate was associated with a significantly higher percentage of abstinent days than placebo (52.3% for placebo, 58.2% for 2 g, 62.7% for 3 g; P=0.01), with an even greater effect in the subgroup of 241 patients having a baseline goal of abstinence (58.1% for placebo, 70.0% for 2 g, 72.5% for 3 g; P=0.02). There were no deaths or serious drug-related adverse events. The US study findings suggest that acamprosate is safe and well tolerated in a broadly inclusive sample of alcoholics and appears effective in populations of patients motivated to have a treatment goal of abstinence.

Acamprosate↗

PubMed2006

AlQoL 9 for measuring quality of life in alcohol dependence.

AIMS: Quality of life (QoL) is an important factor of outcome tracking and treatment in alcohol misuse. A 9-item QoL scale, AlQoL 9, obtained from the generic SF 36, is proposed as a measure that characterizes the QoL of alcohol-dependent patients. Our objective was to study the psychometric properties of this subscale. METHODS: AlQoL 9 was evaluated in two study groups of patients with DSM-IV diagnosis of dependence: 104 inpatients, and 114 outpatients. Severity of dependence, alcohol consumption, psychiatric, and somatic comorbidities were assessed. We studied the global properties of AlQoL 9 and its structure. RESULTS: Cronbach alpha-coefficients in both populations indicated good internal consistency (0.71 and 0.85). Test-retest intraclass coefficients for a 2-day interval in hospital were in the range 0.57-0.78. Principal component analysis found a unidimensional scale. This subscale has properties that are consistent with the concept of QoL in alcohol dependence, i.e. lowered QoL compared with the general population, influenced by gender, and depression. CONCLUSIONS: AlQoL 9 epitomizes QoL in alcohol-dependence. It gives a global measurement with good psychometric properties. It could be used in clinical practice as a diagnosis and management support instrument and may also be useful in research for evaluating treatment efficacy.

Adolescent↗

PubMed2005

Sexuality.

This article reviews changes in sexual function in middle-aged women and discusses how these changes relate to aging, hormone alterations, and psychosocial and physical factors. A Medline search of population-based studies that measured sexual function, menopausal status and/or hormone levels was conducted. Longitudinal findings are from the Melbourne Women's Midlife Health Project, a population-based sample of 438 Australian-born white women, aged 45 to 55 years, who were menstruating at baseline. Annual assessments included hormone levels and the Short Personal Experiences Questionnaire. Few of the population-based studies of the menopausal transition measured sexual function or hormones. Aging and the length of the woman's relationship with her partner are associated with decline in sexual function. An additional decrement in sexual function occurs in midlife associated with menopause. Findings from the Melbourne Women's Midlife Health Project using structural equation modeling, found the most important factors influencing a woman's sexual function are prior level of sexual function; losing or gaining a sexual partner; feelings toward a partner; and estradiol level. When psychosocial and lifestyle status were added to the model, mood was the only additional variable affecting sexual function. There is a decline in all aspects of female sexual function with age. A further incremental decline in most aspects of sexual function occurs as women pass through the menopausal transition and is related to decreasing estradiol levels. Other factors such as prior sexual function and partner issues have larger effects on women's sexual function than do hormonal factors.

Aging↗

PubMed2005

Hot flushes during the menopause transition: a longitudinal study in Australian-born women.

OBJECTIVE: To investigate factors associated with the presence, severity, and frequency of hot flushes. DESIGN: A 9-year prospective study of 438 Australian-born women, aged 45 to 55 years and menstruating at baseline. Annual fasting blood collection, physical measurements, and interviews including questions about bothersome hot flushes in previous 2 weeks were performed. A "hot flush index" score was calculated from the product of the severity and frequency data. Data were analyzed using random-effects time-series regression models. RESULTS: A total of 381 women supplied complete data over the follow-up years. A total of 350 women experienced the menopause transition, of whom 60 (17%) never reported bothersome hot flushes. At baseline, women who reported hot flushes were significantly more likely to have higher negative moods, not be in full- or part-time paid work, smoke, and not report exercising every day. Over the 9-year period of the study, variables significantly associated with reporting bothersome hot flushes were relatively young age (P < 0.001), low exercise levels (P < 0.05), low estradiol levels (P < 0.001), high follicle-stimulating hormone (FSH) levels (P < 0.001), smoking (P < 0.01), being in the late menopause transition (P < 0.001), or being postmenopausal (P < 0.001). In women reporting hot flushes, the hot flush index score increased as their FSH levels increased (P < 0.01), as they entered the late stage of the menopause transition (P < 0.001), and as they became postmenopausal (P < 0.05), and decreased with as their age (P < 0.001) and exercise level (P < 0.05) increased. Between-women analyses found that the hot flush index score was greater in women with higher average FSH levels over time (P < 0.05). CONCLUSION: Menopause status, FSH and estradiol levels, age, exercise level, and smoking status all contributed to the experience of bothersome hot flushes.

Affect↗

PubMed2005

The relative effects of hormones and relationship factors on sexual function of women through the natural menopausal transition.

OBJECTIVE: To investigate the relative effects of hormonal and relationship factors on female sexual function during the natural menopausal transition. DESIGN: Prospective population-based questionnaire study. SETTING: Interviews were conducted in the patients' homes. PATIENT(S): Four hundred thirty-eight Australian-born women aged 45-55 years who were still menstruating at baseline. Eight years of longitudinal data were available for 336 of these women, none of whom were hysterectomized. INTERVENTION(S): Hormonal levels, age, menopausal status, partner status, and feelings for partner were measured and evaluated with longitudinal structural equation modeling. MAIN OUTCOME MEASURE(S): Short personal experiences questionnaire. RESULT(S): Sexual response was predicted by prior level of sexual function, change in partner status, feelings for partner, and E2 level (R2 = .65); dyspareunia was predicted by prior level of dyspareunia and E2 level (R2 = .53); and frequency of sexual activities was predicted by prior level of sexual function, change in partner status, feelings for partner, and level of sexual response (R2 = .52). The minimum effective dose needed to increase sexual response by 10% (700 pmol/L E2) is twice that needed to decrease dyspareunia. CONCLUSION(S): Prior function and relationship factors are more important than hormonal determinants of sexual function of women in midlife.

Female↗

PubMed2005

Investigating the structure of craving using structural equation modeling in analysis of the obsessive-compulsive drinking scale: a multinational study.

BACKGROUND: Currently, there is no agreement among researchers on the definition of craving and its underlying theoretical model. The Obsessive-Compulsive Drinking Scale (OCDS) seems to measure certain aspects of craving, but its theoretical basis remains unclear. The aim of this study was to investigate the structure of alcohol craving, using OCDS data. METHODS: OCDS data from four studies were pooled to obtain a large and heterogeneous sample of 505 participants. All participants were treatment-seeking alcoholics meeting DSM-IV criteria for alcohol dependence. The factor structures of the OCDS previously found were evaluated using confirmatory factor analyses. The goodness of fit of these solutions was compared with those of alternative causal models: an obsessive-compulsive disorder model, an inhibition model, and a cognitive-behavioral model. These alternative models were based on modern theories about craving and were tested in the OCDS data, using structural equation modeling. In this way, the current study replaced simple correlational analysis by a more sophisticated causal way of analyzing the underlying structure of the OCDS items. The best fitting model was selected by comparing the mean discrepancy between the implied and observed matrices of the models. RESULTS: The data showed that the previously reported factor structures had to be rejected. Also, the inhibition model and obsessive-compulsive disorder model did not fit the data. The cognitive-behavioral model showed encouraging fit. Optimizing strategies were applied to further improve the fit of this model, which resulted in a model with close fit to the data. CONCLUSIONS: The causal cognitive-behavioral model proved to be superior. It showed that the OCDS contains many items that do not represent the core concept of craving but instead are indicators for the consequences of craving. From this model, it seems that craving, in a narrow sense, can be reliably assessed with only five items of the OCDS.

Adult↗

PubMed2004

Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients.

RATIONALE: Acamprosate is a proven effective intervention in the treatment of alcohol dependence. However, acamprosate prevents lapses or relapses only in a minority of patients. An important question, therefore, is whether there is a specific subgroup of patients who respond particularly well to acamprosate. OBJECTIVES: To identify predictors of acamprosate efficacy. Based upon the available evidence and hypotheses about the mechanisms underlying acamprosate's effects on drinking behavior, the following variables were considered to be potential positive predictors: high physiological dependence at baseline, negative family history of alcoholism, late age-of-onset, serious anxiety symptomatology at baseline, severe craving at baseline, and female gender. METHOD: Potential predictors of acamprosate's efficacy were analyzed in a pooled analysis of data from seven randomized placebo-controlled trials involving a total of 1485 patients with alcohol dependence. Outcome is measured in terms of cumulative abstinence duration (CAD), continuous abstinence (ABST), and time to first relapse (TFR). RESULTS: CAD and ABST were predicted by baseline measures of craving and anxiety, as well as by study and treatment condition. Acamprosate efficacy was not differentially associated with any of the predictor variables. Importantly, the hypotheses were rejected despite the large sample size and sufficient statistical power. COMMENT: The most straight-forward clinical implication of this study is that acamprosate can be considered as a potentially effective pharmacotherapy for all patients with alcohol dependence. The effect size of acamprosate alone is, however, moderate. Some evidence indicates that the combination of acamprosate with naltrexone or disulfiram leads to substantially better outcomes.

Acamprosate↗

PubMed2004

A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care.

AIMS: To assess the effectiveness of pharmacotherapy with acamprosate in alcohol-dependent patients treated in a naturalistic setting in primary care in France. METHODS: The ARES (Acamprosate et Repercussions Economiques et Sociales; Acamprosate and Economic and Social Repercussions) study was performed by 149 general practitioners interested in treating alcohol use disorders in France who included patients fulfilling DSM-IV criteria for alcohol dependence. The only exclusion criteria concerned contra-indications to acamprosate, co-medication with naltrexone and multiple substance abuse. Eligible patients were randomized to one of two treatment arms, either standard care alone or standard care with acamprosate, using an open-label design and followed up quarterly for a period of 1 year. The primary outcome variable was the change from baseline on the Alcohol-Related Problems Questionnaire. Secondary efficacy variables were abstinence, Clinical Global Impression, quality of life measured with the SF-36 and incidence of adverse events. An intent-to-treat population was used for outcome analysis. RESULTS: 422 patients were included, of whom 348 (82%) completed the protocol as planned. At the end of the study, patients randomized to the acamprosate group had significantly better outcomes in terms of total ARPQ score, change from baseline (-2.61 vs -3.44) and number of subjects with no alcohol-related problem. On average, patients treated with acamprosate had one less alcohol-related problem than did the controls. The number needed to treat in order to save one additional patient from alcohol-related problems compared to standard care was 7.14. Statistically significant differences in favour of the acamprosate group were observed for all secondary efficacy outcome measures including quality of life. CONCLUSIONS: Adjunctive therapy with acamprosate in primary care is associated with significantly better functional outcome. Pragmatic trials in alcohol dependence are both feasible and informative.

Acamprosate↗

PubMed2004

The relative effect of endogenous estradiol and androgens on menopausal bone loss: a longitudinal study.

OBJECTIVE: The aim of this study was to assess the relative strength of the association of endogenous estradiol and androgens with bone loss at the lumbar spine and femoral neck during the menopausal transition. DESIGN: A longitudinal study of a population-based cohort of 159 Australian-born women who at baseline had a mean age of 50.0 years (SD=2.4) and had menstruated in the prior 3 months. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck on up to three occasions. RESULTS: Of the 159 participants, 50 had two BMD measurements and 109 had a third measure. The mean time between the first and final measures for the whole group was 39 months and at the time of the final measures 49% of the participants had become postmenopausal. The mean percentage change/year in lumbar spine BMD was -0.9% (95% CI, -1.1 to -0.6) and at the femoral neck, -0.5% (95% CI, -0.7 to -0.2). A highly significant association with estradiol at the final time point was found, whereas the contribution of estradiol at baseline was negligible. The variance explained by estradiol levels was 19% and 11% for change in BMD at the LS and FN, respectively. Excluding baseline estradiol values and using the average of change in BMD at the LS and FN, the final regression equation estimated that an estradiol level of 330 pmol/l (95% CI, 274 to 386) and 245 pmol/l (95% CI, 194 to 296) is required for preservation of LS and FN BMD, respectively. A stepwise linear regression model was used to assess the effect of age, BMI, estradiol, testosterone, DHEAS, SHBG, and free testosterone index on changes in BMD and found that only the final estradiol level had a significant association with change in BMD. CONCLUSION: Endogenous estradiol was the only hormone among those investigated to have a significant effect on bone mineral density during the menopausal transition.

Bone Density↗

PubMed2004

Parkinson's disease home diary: further validation and implications for clinical trials.

We provide further validation of a Parkinson's disease (PD) home diary and explore implications for practical use in clinical trials. We previously developed and published a home PD diary that includes the categories ASLEEP, off, on without dyskinesia, on with nontroublesome dyskinesia, and on with troublesome dyskinesia [Hauser et al., J Clin Neuropharmacol 2000;23:75-81] and demonstrated that patients generally consider off time and on time with troublesome dyskinesia "bad time" and on time without dyskinesia or with nontroublesome dyskinesia "good time". We suggested that that on time without dyskinesia or with nontroublesome dyskinesia would be an appropriate outcome measure in clinical trials of advanced PD patients. In the current study, PD patients with motor fluctuations and dyskinesia (present more than 25% of the awake day and at least moderately disabling) completed daily diaries on 3 consecutive days in each of 2 consecutive weeks. In addition, patients provided responses to five questions regarding dyskinesia and their motor response through the day on visual analog scales (VAS). Three hundred two patients from 10 countries participated. Eighty-three percent (n = 252) completed six diaries without missing or duplicate entries. Seventy-six percent of the missing or duplicate entries occurred after Day 3. Mean percent of the awake day on without dyskinesia or with nontroublesome dyskinesia ("good on", ONG%) was observed to be very stable over time (repeated measure analysis of variance, P = 0.99). Coefficients of reliability as calculated by Cronbach's alpha were as follows: 2 days, r = 0.806; 3 days, r = 0.868; 4 days, r = 0.918; 5 days, r = 0.934; 6 days, r = 0.946. The standard error of measurement (SEM) was calculated to be 10.75%. VAS responses to the question, "How much of the day today did you experience a good response?" more strongly correlated with ONG% (0.41) than ON% (0.24). The diary appears to be sufficiently simple and feasible. Test-retest reliability was good, and reliability increased with increasing number of diary days but compliance diminished beyond 3 days. Good on time (ONG = on time without dyskinesia or with nontroublesome dyskinesia) most strongly correlated with patients' perceived duration of a good response through the day and is an important outcome variable.

Adult↗

PubMed2004

Improvement in quality of life after treatment for alcohol dependence with acamprosate and psychosocial support.

BACKGROUND: The impact of disease on health-related quality of life is now well recognized, as is the importance of this variable as a measure of treatment efficacy. METHODS: Patients from five European countries were enrolled in an open, multicenter, prospective study designed to observe outcome in dependent drinkers treated for 6 months with acamprosate and psychosocial support. Version 1 of the 36-item Short Form Health Profile (SF-36v1) questionnaire was administered at inclusion and at 3 and 6 months. Responses were described as handicaps compared with an appropriately matched, healthy reference population. One-way fixed ANOVA and simultaneous stepwise linear regression analysis were used to identify potential predictors of quality of life at baseline and after treatment. RESULTS: Baseline SF-36v1 data were obtained from 1216 patients (mean age, 43 +/- 9 years; 77% male). Mean values for all SF-36v1 dimensions were significantly lower in the patient population than in the normative reference population; the most important deficits were observed in physical and emotional role limitations and in social functioning. The most important predictors of baseline quality of life were severity of alcohol dependence, employment status, psychiatric history, quantity and frequency of alcohol consumption, attendance at Alcoholics Anonymous, global alcohol health status, age, gender, and education. SF-36v1 data were obtained from 686 patients at 3 months and from 497 at 6 months. Significant improvements were observed in all SF-36v1 dimensional and summary scores after 3 months of treatment (p < 0.001); further marginal improvements were observed between 3 and 6 months. The most important predictors of quality of life following treatment were the SF-36v1 profile at baseline, followed by abstinence duration; patients who completed the trial and remained abstinent throughout showed the greatest improvement. CONCLUSIONS: Health-related quality of life is severly impaired in dependent drinkers. Treatment with acamprosate and psychosocial support, by promoting abstinence, improves the quality of life profile to levels comparable to those observed in healthy individuals.

Acamprosate↗

PubMed2004

The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis.

BACKGROUND: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. METHODS: All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). RESULTS: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8-18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90-8.82]; p = 0.0106). CONCLUSION: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals.

Acamprosate↗

PubMed2003

Does acamprosate improve reduction of drinking as well as aiding abstinence?

The study aimed to discover whether acamprosate reduces the severity of relapse for those patients undergoing abstinence-orientated treatment who are unable to abstain completely. Data on patients' alcohol consumption from 15 placebo-controlled treatment studies (n = 3309) were examined to test whether, at a given time point, patients who have taken one or more drinks since the last assessment ('relapsers', n = 1010) take alcohol on fewer days, report lower average number of drinks per day, and consume less alcohol in total with acamprosate compared to placebo. These studies had varying duration (90 days, 180 days and 360 days). There were four dates that were common to some studies (days 30, 90, 180 and 360). Among relapsers, acamprosate was significantly associated with less quantity (Q) and frequency (F) of drinking compared to placebo in each of the four follow-up periods (p < 0.001). The differences were most marked for the product Q x F (overall weekly consumption). For each period, there were fewer who were drinking an average of five or more drinks per day in the acamprosate compared to the placebo groups. Acamprosate helps reduce the severity of relapse in patients undergoing abstinence-orientated treatment.

Acamprosate↗

PubMed2002

The European NEAT program: an integrated approach using acamprosate and psychosocial support for the prevention of relapse in alcohol-dependent patients with a statistical modeling of therapy success prediction.

BACKGROUND: A multicenter, prospective study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. METHODS: Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated, for 24 weeks, with acamprosate and appropriate psychosocial support. Potential predictor variables were recorded at inclusion. Drinking behavior was monitored throughout; the proportion of cumulative abstinence days was the principal outcome measure. The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis. Adverse events were recorded systematically. RESULTS: A total of 1289 patients were recruited; 1230 took at least one dose of the drug and provided at least one set of follow-up data; 543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant ( < 0.001) but less so when adjusted for the predictive factors identified in the multivariate model ( < 0.019). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients, being the most frequent. CONCLUSIONS: This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of standard patient care. Treatment benefit was observed irrespective of the nature of the psychosocial support provided. Predictors of the response to treatment were identified; their heterogeneous distribution within the study population explained, at least in part, the differences in outcome between countries.

Acamprosate↗

PubMed2002

Combination of insulin and metformin in the treatment of type 2 diabetes.

OBJECTIVE: To investigate the metabolic effects of metformin, as compared with placebo, in type 2 diabetic patients intensively treated with insulin. RESEARCH DESIGN AND METHODS: Metformin improves glycemic control in poorly controlled type 2 diabetic patients. Its effect in type 2 diabetic patients who are intensively treated with insulin has not been studied. A total of 390 patients whose type 2 diabetes was controlled with insulin therapy completed a randomized controlled double-blind trial with a planned interim analysis after 16 weeks of treatment. The subjects were selected from three outpatient clinics in regional hospitals and were randomly assigned to either the placebo or metformin group, in addition to insulin therapy. Intensive glucose monitoring with immediate insulin adjustments according to strict guidelines was conducted. Indexes of glycemic control, insulin requirements, body weight, blood pressure, plasma lipids, hypoglycemic events, and other adverse events were measured. RESULTS: Of the 390 subjects, 37 dropped out (12 in the placebo and 25 in the metformin group). Of those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with improved glycemic control (mean daily glucose at 16 weeks 7.8 vs. 8.8 mmol/l, P = 0.006; mean GHb 6.9 vs. 7.6%, P < 0.0001); reduced insulin requirements (63.8 vs. 71.3 IU, P < 0.0001); reduced weight gain (-0.4 vs. +1.2 kg, P < 0.01); and decreased plasma LDL cholesterol (-0.21 vs. -0.02 mmol/l, P < 0.01). Risk of hypoglycemia was similar in both groups. CONCLUSIONS-In type 2 diabetic patients who are intensively treated with insulin, the combination of insulin and metformin results in superior glycemic control compared with insulin therapy alone, while insulin requirements and weight gain are less.

Adult↗

PubMed2002

The benefits of metformin therapy during continuous subcutaneous insulin infusion treatment of type 1 diabetic patients.

OBJECTIVE: This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period. RESULTS: Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of -4.3 +/- 9.9 units (-7.8 +/- 18%) compared with an increase with placebo treatment of 1.7 +/- 8.3 units (2.8 +/- 12.7%) (P = 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of -2.6 +/- 3.2 units (-7.9 +/- 23.8%) compared with an increase with placebo treatment of 1.9 +/- 5.7 units (8.8 +/- 27.1%) (P = 0.023). HbA(1c) remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (<60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P = 0.069). CONCLUSIONS: Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.

Adult↗

PubMedDate not supplied

Modeling mid-aged women's sexual functioning: a prospective, population-based study.

This article uses a prospectively, annually collected sexuality questionnaire from an 8-year study of 340 mid-aged Melbourne women. We modeled the interactions of sexuality domains, the effect of prior level of sexual functioning, and the effects of change in partner-related factors. We found that we were unable to separate items denoting sexual interest from those denoting responsiveness. Using the statistical technique of auto-correlation, we determined that the most important predictor of female sexual functioning is prior level of sexual functioning. Partner-related factors (change in partner status and feelings for partner) also had significant effects.

Adaptation, Psychological↗

PubMedDate not supplied

Challenges to medications development in treating alcohol dependence: an international perspective.

Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions. Due to the heterogeneous nature of alcohol dependence, the effort of developing an efficacious medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should enable the appropriate choice of drinking endpoint. The pharmaceutical industry in collaboration with academia might need to develop new approaches to determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market.

Alcoholism↗