Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.

Epidemiology and prevention of cardiovascular disease in the Seychelles Islands (Indian Ocean)

This article presents selected findings and lessons from a cardiovascular research and prevention program initiated in 1989 in the Republic of Seychelles, a country in demographic and epidemiological transition. Rapid and sustained aging of the population (e.g., two-fold increase of people aged 30-39 from 1979 to 1995) implies, over the next few decades, further dramatic increase of the burden of chronic diseases, particularly cardiovascular disease (CVD). Epidemiological surveillance shows high age-specific rates of CVD (particularly stroke), high prevalence of peripheral atherosclerosis (plaques in carotid and femoral arteries), high prevalence of classical modifiable risk factors in the adult population (particularly hypertension), and substantial proportions of children with overweight. Stagnant life expectancy in men and an increase in women have been observed over the last two decades; this occurred despite largely improved health services and reduced infant mortality rates, and may reflect the large CVD burden found in middle-aged men (less so in middle-aged women). A national program of prevention of CVD has been initiated since 1991, which includes a mix of interventions to reduce risk factors in the general population and in high-risk individuals. Substantial research to back the prevention program indeed shows, at the moment, epidemiological patterns in Seychelles similar to those observed in Western countries (e.g., an association between peripheral atherosclerosis [as a proxy of CVD] and low density lipoprotein-cholesterol, smoking, diabetes, and [inversely] walking). This clearly supports the view that promotion of healthy lifestyles and control of conventional risk factors should be the main targets for CVD prevention and control.

The relationship between subjective experiences during first use of tobacco and cannabis and the effect of the substance experienced first.

INTRODUCTION: We examined the positive and negative subjective feelings associated with initial tobacco and cannabis use as well as the role of these experiences in regular use. Additionally, we investigated the effect of the first substance experienced on initial subjective experiences and later regular use. METHODS: Baseline data from a representative sample of young Swiss men were obtained from an ongoing Cohort Study on Substance Use Risk Factors, which includes 2,321 lifetime tobacco and cannabis users. We assessed the age of first tobacco and cannabis use along with the subjective experiences associated with initial use. Additionally, subjective experiences related to regular use of both substances were analyzed. RESULTS: The initial subjective experiences were divided into positive and negative for each substance, and we found that the feelings associated with first use of tobacco and cannabis were similar. Moreover, the participants who used cannabis before tobacco reported fewer negative experiences associated with first tobacco use, whereas the participants who initially used tobacco reported more negative experiences related to first cannabis use. Also, we identified that regular use was encouraged by positive experiences and that negative experiences were more adverse for regular use of cannabis compared with tobacco. CONCLUSIONS: Taken together, these results indicate that similar subjective experiences were associated with the first use of tobacco and cannabis. Also, the use of cannabis before tobacco, which occurred in only a minority of users, had the potential to enhance the effects of initial tobacco use.

Some go without a cigarette: characteristics of cannabis users who have never smoked tobacco.

OBJECTIVES: To estimate the prevalence of youth who use cannabis but have never been tobacco smokers and to assess the characteristics that differentiate them from those using both substances or neither substance. DESIGN: School survey. SETTING: Postmandatory schools. PARTICIPANTS: A total of 5263 students (2439 females) aged 16 to 20 years divided into cannabis-only smokers (n = 455), cannabis and tobacco smokers (n = 1703), and abstainers (n = 3105). OUTCOME MEASURES: Regular tobacco and cannabis use; and personal, family, academic, and substance use characteristics. RESULTS: Compared with those using both substances, cannabis-only youth were younger (adjusted odds ratio [AOR], 0.82) and more likely to be male (AOR, 2.19), to play sports (AOR, 1.64), to live with both parents (AOR, 1.33), to be students (AOR, 2.56), and to have good grades (AOR, 1.57) and less likely to have been drunk (AOR, 0.55), to have started using cannabis before the age of 15 years (AOR, 0.71), to have used cannabis more than once or twice in the previous month (AOR, 0.64), and to perceive their pubertal timing as early (AOR, 0.59). Compared with abstainers, they were more likely to be male (AOR, 2.10), to have a good relationship with friends (AOR, 1.62), to be sensation seeking (AOR, 1.32), and to practice sports (AOR, 1.37) and less likely to have a good relationship with their parents (AOR, 0.59). They were more likely to attend high school (AOR, 1.43), to skip class (AOR, 2.28), and to have been drunk (AOR, 2.54) or to have used illicit drugs (AOR, 2.28). CONCLUSIONS: Cannabis-only adolescents show better functioning than those who also use tobacco. Compared with abstainers, they are more socially driven and do not seem to have psychosocial problems at a higher rate.

Representation of motor habit in a sequence of repetitive reach and grasp movements performed by macaque monkeys: evidence for a contribution of the dorsolateral prefrontal cortex.

In the context of an autologous cell transplantation study, a unilateral biopsy of cortical tissue was surgically performed from the right dorsolateral prefrontal cortex (dlPFC) in two intact adult macaque monkeys (dlPFC lesioned group), together with the implantation of a chronic chamber providing access to the left motor cortex. Three other monkeys were subjected to the same chronic chamber implantation, but without dlPFC biopsy (control group). All monkeys were initially trained to perform sequential manual dexterity tasks, requiring precision grip. The motor performance and the prehension's sequence (temporal order to grasp pellets from different spatial locations) were analysed for each hand. Following the surgery, transient and moderate deficits of manual dexterity per se occurred in both groups, indicating that they were not due to the dlPFC lesion (most likely related to the recording chamber implantation and/or general anaesthesia/medication). In contrast, changes of motor habit were observed for the sequential order of grasping in the two monkeys with dlPFC lesion only. The changes were more prominent in the monkey subjected to the largest lesion, supporting the notion of a specific effect of the dlPFC lesion on the motor habit of the monkeys. These observations are reminiscent of previous studies using conditional tasks with delay that have proposed a specialization of the dlPFC for visuo-spatial working memory, except that this is in a different context of "free-will", non-conditional manual dexterity task, without a component of working memory.

First use of multiple substances: Identification of meaningful patterns

Context: Understanding the process through which adolescents and young adults are trying legal and illegal substances is a crucial point for the development of tailored prevention and treatment programs. However, patterns of substance first use can be very complex when multiple substances are considered, requiring reduction into a few meaningful number of categories. Data: We used data from a survey on adolescent and young adult health conducted in 2002 in Switzerland. Answers from 2212 subjects aged 19 and 20 were included. The first consumption ever of 10 substances (tobacco, cannabis, medicine to get high, sniff (volatile substances, and inhalants), ecstasy, GHB, LSD, cocaine, methadone, and heroin) was considered for a grand total of 516 different patterns. Methods: In a first step, automatic clustering was used to decrease the number of patterns to 50. Then, two groups of substance use experts, three social field workers, and three toxicologists and health professionals, were asked to reduce them into a maximum of 10 meaningful categories. Results: Classifications obtained through our methodology are of practical interest by revealing associations invisible to purely automatic algorithms. The article includes a detailed analysis of both final classifications, and a discussion on the advantages and limitations of our approach.

Can a Lucas model with habit generate realistic conditional volatility in exchange rate returns?

In this paper, we attempt to give a theoretical underpinning to the well established empirical stylized fact that asset returns in general and the spot FOREX returns in particular display predictable volatility characteristics. Adopting Moore and Roche s habit persistence version of Lucas model we nd that both the innovation in the spot FOREX return and the FOREX return itself follow "ARCH" style processes. Using the impulse response functions (IRFs) we show that the baseline simulated FOREX series has "ARCH" properties in the quarterly frequency that match well the "ARCH" properties of the empirical monthly estimations in that when we scale the x-axis to synchronize the monthly and quarterly responses we find similar impulse responses to one unit shock in variance. The IRFs for the ARCH processes we estimate "look the same" with an approximately monotonic decreasing fashion. The Lucas two-country monetary model with habit can generate realistic conditional volatility in spot FOREX return.

The Change Questionnaire predicts change in hazardous tobacco and alcohol use.

INTRODUCTION: Assessing motivation for change is deemed an important step in the treatment process that allows further refinement of the intervention in motivational interviewing (MI) and brief MI (BMI) adaptations. During MI (and BMI) sessions, motivation for change is expressed by the client as "change talk", i.e. all statements inclined toward or away from change. We tested the predictive validity of the Change Questionnaire, a 12-item instrument assessing motivation to change, on hazardous tobacco and alcohol use. METHODS: As part of the baseline measurements for a randomized controlled trial on multi-substance BMI at the Lausanne recruitment center (army conscription is mandatory in Switzerland for males at age 20, and thus provides a unique opportunity to address a non-clinical and largely representative sample of young men), 213 participants completed the questionnaire on tobacco and 95 on alcohol and were followed-up six months later. The overall Change Questionnaire score and its six subscales (Desire, Ability, Reasons, Need, Commitment, and Taking steps) were used as predictors of hazardous tobacco use (defined as daily smoking) and hazardous alcohol use (defined as more than one occasion with six standard drinks or more per month, and/or more than 21 standard drinks per week) in bivariate logistic regression models at follow-up. RESULTS: Higher overall Change scores were significant predictors of decreased risk for hazardous tobacco (odds ratio [OR] = 0.83, p = 0.046) and alcohol (OR = 0.76, p = 0.03) use. Several sub-dimensions were associated with the outcomes in bivariate analyses. Using a principal components analysis to reduce the number of predictors for multivariate models, we obtained two components. 'Ability to change' was strongly related to change in hazardous tobacco use (OR = 0.54, p < 0.001), the second we interpreted as 'Other change language dimensions' and which was significantly related to change in hazardous alcohol use (OR = 0.81, p = 0.05). CONCLUSIONS: The present findings lend initial support for the predictive validity of the Change Questionnaire on hazardous tobacco and alcohol use, making it an interesting and potentially useful tool for assessing motivation to change among young males.

ADOS: an educational primary prevention programme for preventing excess body weight in adolescents.

OBJECTIVE: The prevalence of adolescent obesity has increased considerably over the past decade in Switzerland and has become a serious public health problem in Europe. Prevention of obesity using various comprehensive programmes appears to be very promising, although we must admit that several interventions had generally disappointing results compared with the objectives and target initially fixed. Holistic programmes including nutritional education combined with promotion of physical activity and behaviour modification constitute the key factors in the prevention of childhood and adolescent obesity. The purpose of this programme was to incorporate nutrition/physical education as well as psychological aspects in selected secondary schools (9th grade, 14-17 years). METHODS: The educational strategy was based on the development of a series of 13 practical workshops covering wide areas such as physical inactivity, body composition, sugar, energy density, invisible lipids, how to read food labels, is meal duration important? Do you eat with pleasure or not? Do you eat because you are hungry? Emotional eating. For teachers continuing education, a basic highly illustrated guide was developed as a companion booklet to the workshops. These materials were first validated by biology, physical education, dietician and psychologist teachers as well as school medical officers. RESULTS: Teachers considered the practical educational materials innovative and useful, motivational and easy to understand. Up to now (early 2008), the programme has been implemented in 50 classes or more from schools originating from three areas in the French part of Switzerland. Based on the 1-week pedometer value assessed before and after the 1 school-year programme, an initial evaluation indicated that overall physical placidity was significantly decreased as evidenced by a significant rise in the number of steps per day. CONCLUSION: Future evaluation will provide more information on the effectiveness of the ADOS programme.

Prevention and treatment options for postoperative delirium in the elderly.

PURPOSE OF REVIEW: To review recent findings and developments in strategies for prevention and treatment of postoperative delirium. RECENT FINDINGS: Current advances in the field include improved knowledge about predisposing and precipitating factors, evidence for efficacy of multicomponent prevention programmes, refinement of perioperative procedures, and promising pharmacological approaches for prophylaxis and management of postoperative delirium. SUMMARY: Postoperative delirium is a common and serious complication in elderly patients. Preoperative assessment of risk profiles and tailored multimodal prevention approaches proved effective and should be integrated into clinical practice. Despite promising recent findings, at present, the routine use of pharmacological prophylaxis cannot be recommended. Validated and easy-to-use bedside diagnostic tools are available and should be regularly applied for delirium screening in the first days after surgery. In patients developing delirium, causal conditions and contributing factors need to be identified and addressed. Whereas administration of antipsychotics may represent an option for symptomatic treatment, further studies are needed to evaluate the effects of pharmacological approaches on long-term outcomes in elderly patients with delirium.

Administering brief motivational interventions to young men: Results from a pilot census transmissible study among 19 year-old francophone Swiss men.

AIMS - To pilot the implementation of brief motivational intervention (BMI) among conscripts, and to test the effectiveness of BMI in young men voluntarily showing up for a single face-to-face alcohol BMI session. Participants were conscripts attending the army recruitment process in Lausanne. This process is mandatory for all Swiss males at age 19 and Lausanne serves all francophone Swiss men. METHODS - Of 3'227 young men that were seen during the army recruitment procedures, 445 voluntarily showed up for a BMI and 367 were included in the study (exclusions were random and unsystematic and related to organizational aspects in the recruitment center). After an initial assessment, subjects were randomized into two groups: an immediate BMI and a 6-month delayed BMI (waiting list design). A 6-month follow-up assessment was conducted in both groups. BMI was a face-to-face 20 minutes counseling session with a psychologist trained in motivational interviewing at baseline and a telephone session for the control group at follow-up. Strategies of BMI included the exploration and evocation of a possible behavior change, importance of future change, readiness to change, and commitment to change. A filmed example of such an intervention is available in French at www.alcoologie.ch. RESULTS - All procedures are now fully implemented and working and the provision of preventive efforts found general approval by the army. 3'227 were eligible for BMI and 445 of them (13.8%) showed up for receiving a BMI. 367 were included in the study, 181 in the BMI group and 186 in the control group. More than 86% of those included were reached at follow-up. With one exception all findings on alcohol use went in the expected direction, i.e. a stronger decrease in alcohol use (or a smaller increase as for usual weekly drinking amount) in the BMI group. The risk for risky single occasion drinking (RSOD) decreased from 57% at-risk users at baseline to 50.6%, i.e. a 6.4% point decrease in the BMI group, while there was only a 0.6% point decrease (from 57.5% to 56.9%) in the control group. Moreover, the study showed that there was a likelihood of crossover effects for other substances like tobacco smoking and cannabis use. Despite these encouraging and consistent positive findings, none reached significance at conventional levels (p < 0.05). DISCUSSION - Data suggest a beneficial impact of BMI on alcohol use outcomes and potential effect on other substance use in 19-year old men attending the army recruitment and showing up voluntarily for BMI. As the main aim was to implement and test feasibility of conducting BMI in this setting none of our findings reached statistical significance. The consistency of findings across measures and substances, however, raises hope that non-significance in the present study does not mean no effect, but mainly insufficient power of this pilot study. [Authors]