Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men

OBJECTIVE: To explore effects on serum lipids, pituitary-gonadal axis, prostate and bone turnover of the administration of the mixed oestrogen agonist/antagonist raloxifene in healthy elderly men. PARTICIPANTS: Thirty healthy men aged 60-70 years randomly received raloxifene 120 mg/day (n=15) or placebo (n=15) for 3 months. MEASUREMENTS: In this double-blind, placebo-controlled study, serum gonadotrophins, sex hormones, prostate specific antigen (PSA), a marker of bone turnover, urinary hydroxyproline (OHPro) and cholesterol were measured at baseline and after 3 months. RESULTS: Raloxifene significantly increased serum concentrations of LH and FSH (by 29% and 21%), total testosterone (20%), free testosterone (16%) and bioavailable testosterone (not bound to sex hormone-binding globulin (SHBG; 20%). In parallel with testosterone, 17 beta-oestradiol also increased by 21%. SHBG increased by 7%. Total cholesterol (TChol) decreased significantly, from 5.7 to 5.5 mmol/l (P=0.03). Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) showed a trend to decrease. Overall, there was no change in urinary OHPro/creatinine ratio as a marker for bone resorption. However, the raloxifene-induced increases in both serum testosterone and 17 beta-oestradiol were significantly related to a lower OHPro/creatinine ratio. Total PSA increased by 17% without significant changes in free PSA or free/total PSA ratio. Participants reported no side effects and raloxifene was well tolerated. CONCLUSION: In healthy elderly man, raloxifene 120 mg/day for 3 months increased LH, FSH and sex steroid hormones. Potentially beneficial effects were the small but significant decrease in TChol and the trend towards a decrease in LDL-c. Negative effects were the trend towards a decrease in HDL-c and the significant increase in serum PSA. A decrease in markers of bone resorption during raloxifene treatment was found only in men with relatively high increases in serum testosterone and 17 beta-oestradiol. Overall, there were no clear beneficial effects of administration of raloxifene to ageing men in this preliminary investigation.     

Causes and prognosis of syncope in patients with primary dilated cardiomyopathy

The causes of adverse prognosis of patients with primary dilated cardiomyopathy remain controversial. Classically, it is thought that syncope is associated with an increased risk of mortality. The aim of this study was to try and identify the causes and prognostic significance of syncope in patients with primary dilated cardiomyopathy. Sixty-five patients aged 31 to 80 with primary dilated cardiomyopathy were admitted for investigation of syncope. The average ejection fraction was 27 +/- 10%. Invasive and non-invasive investigations including complete electrophysiological investigations, were performed. Sustained monomorphic ventricular tachycardia was induced in 14 patients (21.5%), ventricular flutter or fibrillation was induced in 9 patients (14%), a supraventricular arrhythmia in 17 patients (26%), and a conduction defect alone or associated with another arrhythmia in 7 patients (11%). A pathological result of tilt testing was observed in 5 patients (8%). No cause of syncope could be demonstrated in 15 patients (23%). During follow-up (4 +/- 2 years) there was a mortality of 15% which was only correlated with the reduction in left ventricular ejection fraction. The authors conclude that there are many causes of syncope in primary dilated cardiomyopathy: ventricular arrhythmias represent only 35% of cases and do not impact on the prognosis; above all, left ventricular ejection fraction is the most important prognostic factor.     

Preference assessment procedures for individuals with developmental disabilities

Significant advancements have been made in the development of procedures to systematically identify preferred stimuli that may function as reinforcers for persons with developmental disabilities. Indirect assessment procedures include care provider and client interviews, whereas direct assessment procedures involve systematically exposing participants to stimuli while recording their responses. These types of direct assessment procedures can be categorized as either approach-based or engagement-based. Approach-based procedures involve recording the individuals' approach responses to stimuli presented singly or concurrently with other stimuli, whereas engagement-based procedures involve recording duration of engagement with stimuli. Although the predictive validity of indirect preference assessment procedures has yet to be established, using them in combination with direct measures of preference may be most efficacious for identifying potential reinforcers. Recent research on preference assessment procedures used with persons with developmental disabilities is reviewed and the variables that one might consider prior to selecting which procedure to use in a given situation are discussed.     

Emergency department management and outcome for self-poisoning: a cohort study

Self-poisoning in adults is an important public health problem across the world, but evidence to guide psychological management is lacking. In the current cohort study we wished to investigate whether aspects of routine Emergency Department management such as receiving a psycho-social assessment, or being referred for specialist follow up, affected the rate of repetition of self-poisoning. The study was carried out in four inner city hospitals in Greater Manchester, United Kingdom, over a 5-month period. We used hospital information systems and reviewed the case notes of every patient presenting to the Emergency Department to identify prospectively all adult patients presenting with deliberate self-poisoning. Data regarding the Emergency Department management of each episode were collected. The Manchester and Salford self-harm database was used to determine the number of individuals who went on to repeat self-poisoning within 6 months of their index episode. During the recruitment period 658 individuals presented with self-poisoning. Traditional risk factors for repetition such as substance dependence, psychiatric contact, and previous self-poisoning were associated with a greater likelihood of receiving a psycho-social assessment or being referred for specialist follow-up. Ninety-six patients (14.6%) repeated self-poisoning within 6 months of their index episode. After adjustment for baseline demographic and clinical characteristics and hospital, receiving a psycho-social assessment was not associated with reduced repetition but being referred for specialist follow-up was [adjusted hazard ratio for repetition (95% CI): 0.49 (0.25 to 0.84), P=.01]. We found that being referred for active follow-up after self-poisoning was associated with a reduced risk of repetition. The implications of this finding are discussed. Further studies using both cohort and randomized controlled study designs will help inform management strategies for patients who poison themselves.     

Common and constrasting areas of activation for abstract and concrete concepts: an H2 15O PET study

Lesion studies indicate that the lateral and inferior temporal cortex is a critical area of semantic memory storage, but little is known about the cortical organization of semantics within this area. One proposition has been that dominant physical characteristics of objects (structure, motility) are determining factors. A positron emission tomography experiment using the H2(15)O bolus method was performed to test this hypothesis by contrasting activation for concrete and abstract concepts. Unlike previous studies that considered this question, the task required explicit word meaning judgments, and blocks of trials were designed to be of equal difficulty for the two word classes. The task required elderly participants to read aloud the pair of words that was closer in meaning (e.g., spade-shovel vs. spade-carpet). Subtraction analyses that compared the semantic judgment tasks with a baseline condition indicated that both abstract and concrete concepts activated the left lateral temporal cortex. A direct comparison of abstract versus concrete scans indicated differences in the lateralization of fusiform activation. We conclude that although concreteness might be a critical factor in the fusiform cortex, it is not dominant in the lateral temporal cortex. A multistudy overview suggests that tasks that focus on one concept per trial activate areas posterior to y = -40, whereas those that invoke several concepts, as in the present study, activate areas anterior to this. Increased processing complexity may proceed in a posterior-anterior direction in the lateral temporal cortex.     

The psychosocial outcome of pregnancy in women with psychotic disorders

OBJECTIVE: To investigate the psychosocial outcome of pregnancies in women with a history of psychotic disorder in an epidemiologically representative sample and to determine the predictors of having a baby looked after by social services in the first year of life. METHOD: Historical matched controlled cohort study and nested case control study using the General Practice Research Database (GPRD), an anonymised primary care database, in women with a history of psychotic disorders who gave birth in 1996-1998 (199 cases and 787 controls). RESULTS: Twenty-seven percent of cases had a psychotic episode and a further 38% had nonpsychotic depression in the first year after birth. Women with nonaffective psychoses were at a significantly higher risk of postnatal depression compared with controls (adjusted rate ratio 2.07, 95% CI 1.45-2.96, p<0.001). Cases were well supported with 72% in a cohabiting relationship and only 38% on benefits. The only significant predictor of parenting difficulties was recent contact with psychiatric services. CONCLUSIONS: Women with a history of psychotic disorder are at high risk of psychiatric illness postpartum, particularly a twofold risk of postnatal depression, even if they have not been in contact with psychiatric services during pregnancy. However, this epidemiologically representative sample has better parenting outcomes than has been previously reported for specialist treated cases. Liaison between all professionals involved in the care of mothers with psychotic disorders during and after pregnancy is essential to optimise care for them and their families.     

Factors influencing compulsory admission in first-admitted subjects with psychosis

Abstract. Background: There is a growing body of evidence that patients with early psychosis have undesirable pathways to care, yet few studies have explored the factors related to compulsory admission in patients with psychosis. The aim of the present study was to examine the demographic and clinical factors and pathways to care influencing compulsory admission in first-admitted subjects with psychosis. Methods: Pathways to care, clinical and demographic characteristics, were assessed using multiple sources of information in 86 subjects with psychosis first admitted in two hospitals of South-Western France. Characteristics independently associated with compulsory admission were explored using logistic regressions. Results: Nearly two-thirds of the subjects (61.6%) were compulsorily admitted. Compulsory admission was independently predicted by being a male (adjusted OR = 3.2, 95% CI 1.2–8.6, p = 0.02), having a diagnosis of schizophrenia broadly defined (adjusted OR = 2.8, 95% CI 1.02–7.4, p = 0.04) and absence of depressive or anxiety symptoms (adjusted OR = 0.05, 95 % CI 0.005–0.5, p = 0.01). Conclusion: These results suggest that factors related to the disease itself play an important role in decisions concerning compulsory admission. The high frequency of compulsory admission as the first mode of contact with psychiatric hospital in subjects with psychosis constitutes a major public health issue. Further research on the strategies aimed at avoiding compulsory admission in subjects with incipient psychosis is necessary.