Statin lipid-lowering drugs and bone mineral density

BACKGROUND: HMG Co-A reductase inhibitors (statin lipid-lowering drugs) have been associated with a reduced rate of fractures in some studies, but not in others. We examined the relationship between statin use and bone density among postmenopausal women. METHODS: We conducted a cross-sectional survey at one academic medical center. Postmenopausal women who underwent bone densitometry and agreed to a telephone interview were surveyed about osteoporosis risk factors, use of hormone replacement therapy and osteoporosis medications and statin exposure. We then developed linear regression models adjusting for known counfounders to assess the relationship between statin use and bone mineral density (BMD). RESULTS: Of 339 women studied, 162 were current or past users of statins, and 177 were not. Statin users and non-users were similar with respect to age, race, prior fracture history, the presence of medical conditions associated with osteoporosis, use of medications for osteoporosis, use of tobacco and use of oral glucocorticoids. Statin users had significantly higher body mass index (BMI) and rates of thiazide use, and were more likely to abstain from alcohol. After adjusting for important confounders, we found that statin use was associated with a significantly higher t-score at the total hip (-0.53 +/- 0.17) compared with non-users (-0.83 +/- 0.18; p = 0.02). At the lumbar spine, there was a trend toward higher t-scores in statin users (-0.91 +/- 0.24) compared with non-users (-1.21 +/- 0.23; p = 0.08). CONCLUSIONS: These results support the hypothesis that statin use is associated with higher BMD. While it is unclear whether their relationship is causal, further controlled studies examining bone formation and resorption would help determine the clinical implications of these findings.     

Association between total cadmium intake calculated from the cadmium concentration in household rice and mortality among inhabitants of the cadmium-polluted Jinzu River basin of Japan

A follow-up survey was conducted to investigate the relationship between total Cd intake and mortality in the Jinzu River basin for 6128 days among 757 inhabitants who ingested household rice. When the subjects were divided into two groups, standardized mortality ratios (SMRs) were 0.94 in men and 1.36 in women for the > or = 2.0 g group and 0.68 in men and 0.29 in women for the <2.0 g group (significant in the women). Cox's hazard ratios for men, women, and men+women for the > or = 2.0 g group relative to those in the <2.0 g group were 1.406, 3.955 and 1.950 (significant in the men+women). Using total Cd intake as a continuous variable, the hazard ratios were 1.045, 1.146 and 1.049 in men, women, and men+women (significant in the women), respectively. In the Jinzu River basin, increased total Cd intake appears to exert an adverse influence on life prognosis.     

Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs

BACKGROUND: A substantial literature suggests that users of illicit 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") display residual cognitive deficits. Most MDMA users, however, use other illicit drugs as well, so it is difficult to be certain that these deficits are due to MDMA, as opposed to other drug use or additional confounding factors. METHODS: We administered a battery of neuropsychological tests to 23 young MDMA users who reported minimal exposure to any other drugs, including alcohol, and to 16 comparison individuals equally involved with the rave subculture, but reporting no MDMA use. We compared the groups by regression analyses adjusting for numerous potentially confounding variables. To test for a possible dose-response effect, we also performed a median split of 12 moderate MDMA users (22-50 lifetime uses) and 11 heavy users (60-450 uses), and compared these subgroups with non-users. RESULTS: MDMA users as a whole performed worse than non-users on most test measures, but these comparisons rarely reached statistical significance. This picture changed markedly in the subgroup analysis: although moderate users displayed virtually no differences from non-users on any measures, the heavy users displayed significant deficits on many measures, particularly those associated with mental processing speed and impulsivity. These differences did not appear explainable by differences in family-of-origin variables, verbal IQ, levels of depression, or time since last MDMA use. CONCLUSIONS: The presence of residual cognitive deficits, even among unusually "pure" frequent users of illicit MDMA, analyzed with adjustment for confounding variables, augments the evidence that MDMA itself, rather than some associated factor, is responsible for the deficits observed.     

Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment

This is a register-based cohort study of 20,581 individuals in treatment for illicit substance use disorders in Denmark between 1996 and 2006. All in all, 1441 deaths were recorded during 111,445 person-years of follow-up. Standardized mortality ratios (SMRs) associated with different primary substance types were calculated and Cox-regression analyses were performed in order to establish hazard ratios (HR) associated with injection drug use and psychiatric comorbidity. SMRs for primary users of specific substances were: cannabis: 4.9 (95% confidence interval (CI): 4.2-5.8), cocaine: 6.4 (CI: 3.9-10.0), amphetamine: 6.0 (CI: 4.2-8.3), heroin: 9.1 (CI: 8.5-9.8), and other opioids 7.7 (CI: 6.6-8.9). For MDMA ('ecstasy') the crude mortality rate was 1.7/1000 person-years (CI: 0.4-7.0) and the SMR was not significantly elevated. Injection drug use was associated with significantly increased hazard ratios in users of opioids and cocaine/amphetamine. Overall, psychiatric comorbidity was not associated with increased mortality (HR: 1.1 [CI: 0.9-1.2], p=.28), but an association was found specifically among cocaine/amphetamine users (HR: 3.6 [CI: 2.1-6.4], p<.001).     

Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population-based cohort study

AIM

Information from the spontaneous reporting system raised the hypothesis of an increased risk of meningioma in patients treated with high doses of cyproterone acetate (CPA). The objective of this study was to test the hypothesis of an increased risk of meningioma among users of high dose CPA as compared with non-users in a medical records computerized database.

METHODS

A retrospective cohort study was performed in a Spanish primary care database (BIFAP). Meningioma incidence rates were compared in patients exposed to high dose CPA (users) with those non-exposed and with those exposed to low dose CPA. Poisson regression analysis was used to estimate the incidence rate ratios after adjusting for age and gender.

RESULTS

Among 2474 users of high dose cyproterone (6663 person-years) four meningioma cases were identified, resulting in an incidence rate (IR) of 60.0 (95% CI 16.4, 153.7) per 100 000 person-years, which was significantly higher than that observed among the non-users (IR 6.6; 95% CI 6.0, 7.3) and among women users of low dose cyproterone (IR 0.0, 95% CI upper limit 5.5). After adjusting for age and gender, patients exposed to high dose CPA showed an increased risk of meningioma of 11.4 (95% CI 4.3, 30.8) as compared with non-users.

CONCLUSIONS

The results of this study support the hypothesis that the exposure to high dose CPA increases the risk of meningioma.     

Characteristics of ecstasy users in Sãio Paulo, Brazil

The present study was aimed at identifying patterns of Ecstasy (methylenedioxymethamphetamine-MDMA) use in the city of S?o Paulo. Ecstasy users were recruited through the snowball technique. Using the same technique, a non-user control group was recruited among individuals that had never tried the drug but shared with users a similar life style. Users (N = 52) and non-users (N = 52) were interviewed in order to obtain data on socio-demographic characteristics and use of psychoactive drugs. In addition, levels of anxiety, depression and impulsiveness were assessed through Spielberger's IDATE Trace Inventory, Beck's Depression Inventory and Barrat Impulsiveness Scale. Both users and non-users revealed similar socio-demographic characteristics: most subjects were middle class young heterosexual single men and women who had a college degree. Multiple drug use was more frequent among users than among non-users. Other features that were significantly more accentuated among users than among non-users were the presence of tattoos and piercings, the frequency of attending raves and the preference for electronic music. Beck Inventory results pointed to significantly lower depression scores among users. No differences were observed between groups regarding anxiety and impulsiveness scores. Although the use of Ecstasy in S?o Paulo is restricted to a young middle or high social class, their vanguard lifestyle tends to influence youngsters of other social extractions, so that the use of the drug may soon become widespread and thus a legitimate public health concern.     

Characteristics of Ecstasy Users in São Paulo,Brazil

The present study was aimed at identifying patterns of Ecstasy (methylenedioxy-methamphetamine—MDMA) use in the city of São Paulo. Ecstasy users were recruited through the snowball technique. Using the same technique, a non-user control group was recruited among individuals that had never tried the drug but shared with users a similar life style. Users (N = 52) and non-users (N = 52) were interviewed in order to obtain data on socio-demographic characteristics and use of psychoactive drugs. In addition, levels of anxiety, depression and impulsiveness were assessed through Spielberger's IDATE Trace Inventory, Beck's Depression Inventory and Barrat Impulsiveness Scale. Both users and non-users revealed similar socio-demographic characteristics: most subjects were middle class young heterosexual single men and women who had a college degree. Multiple drug use was more frequent among users than among non-users. Other features that were significantly more accentuated among users than among non-users were the presence of tattoos and piercings, the frequency of attending raves and the preference for electronic music. Beck Inventory results pointed to significantly lower depression scores among users. No differences were observed between groups regarding anxiety and impulsiveness scores. Although the use of Ecstasy in São Paulo is restricted to a young middle or high social class, their vanguard lifestyle tends to influence youngsters of other social extractions, so that the use of the drug may soon become widespread and thus a legitimate public health concern.     

The diet of Auckland men and women aged 25-64 years.

The dietary intake of a sample of 537 men and 372 women aged 25-64 years, randomly selected from the Auckland general electoral rolls, was assessed in order to describe current nutritional patterns in Auckland and to compare dietary intakes between men and women. A 118 item food frequency questionnaire was given to each participant to recall usual intake over the previous three months. After adjusting for energy intake, men consumed significantly more fat and cholesterol than women, consistent with their increased intake of red meat (median serves per month = 28 for men, 23 for women) and their greater tendency to eat fried meat (80.3% v 71.7%) and to drink full cream milk (82.7% v 70.7%). In contrast, women consumed more carbohydrate and fibre than men after adjusting for energy, consistent with their increased intake of vegetables (median serves per month = 136 for women, 116 for men) and fruit (median serves per month = 71 for women, 39 for men). These dietary differences between men and women may partly explain the increased coronary heart disease rates in men.     

Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause–effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary β2-microglobulin (β2MG) and N-acetyl-β-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02–1.19, pancreas: HR, 1.10, 95%CI, 1.02–1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67–0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93–1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.     

Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects,cognition and brain function by previous cannabis exposure

Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (?)-trans-Δ9-tetrahydrocannabinol (?9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ?9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ?9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (?9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ?9-THC. Under ?9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ?9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ?9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ?9-THC, which are more marked in people who have never used cannabis.     

Effect of withdrawal from long-term use of temazepam,zopiclone or zolpidem as hypnotic agents on cognition in older adults

Purpose

The aim of this study was to assess the effect of withdrawal from the long-term use of temazepam, zopiclone or zolpidem as hypnotics drugs (here referred to as BZD) on cognitive performance.

Methods

Ninety-two adults (age ≥55 years) with primary insomnia and who were long-term daily users of BZD volunteered to participate in a 1-month medically supported withdrawal attempt from BZD use, with a subsequent 5-month follow-up. Withdrawal was based on plasma BZD measurements at baseline, at 1 month and during subsequent regular clinical appointments. Attention and psychomotor performance were measured using the CogniSpeed® at baseline and at 1, 2 and 6 months. Reaction times were determined in the Simple Reaction Time (SRT), Two-Choice Reaction Time (2-CRT) and Vigilance tests, and errors were measured by the 2-CRT and Vigilance tests. The cognition data of the withdrawal group were also compared with a cohort of BZD non-users.

Results

Eighty-nine (97 %) participants (59 women, 30 men) were followed-up for a maximum of 6 months. During the follow-up period, changes in reaction times and errors did not differ between short-term withdrawers (no residual BZD at 1 month; N?=?69), non-withdrawers (residual BZD at 1 month; N?=?20) or long-term withdrawers (N?=?34). Compared to the reaction times of the BZD-free cohort, those of BZD users were slower at baseline. The reaction times of BZD withdrawers based on the results of the SRT or 2-CRT tests during follow-up did not reach those of the BZD-free cohort, but there was no difference between these groups in the Vigilance test.

Conclusions

Long-term use of BDZ as hypnotic drugs by older adults is related to prolonged impairment of attentional and psychomotor cognitive functioning that persists for at least 6 months after withdrawal.     

Sub-acute effects of MDMA (±3,4-methylenedioxymethamphetamine, "ecstasy") on mood: evidence of gender differences

RATIONALE: Research with animals suggests that central 5-hydroxytryptamine (5-HT) function may be attenuated for a period following a single dose of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). If the same is true in humans, then functions thought to be modulated by 5-HT may differ in MDMA users compared with non-users a few days after the drug is taken. AIMS: The present study therefore investigated both acute and sub-acute effects of MDMA on mood of recreational users. A second aim was to determine whether these effects differ for females and males. DESIGN: A parallel group design was used to compare 40 participants who reported taking MDMA with 40 participants who reported using illicit substances excluding MDMA (polydrug controls). Participants were assessed on the night of drug use (day 0) and again 4 days later. RESULTS: Female MDMA users showed higher depression scores mid-week than male users or male or female controls. Mid-week depression in female users was correlated with the amount of MDMA taken on day 0. MDMA users rated lower levels of aggression than controls on the night of drug use but significantly higher levels of aggression mid-week, and in males change in aggression correlated with the amount of MDMA taken on the weekend. There was no association between mood and measures of long-term use of MDMA (e.g. years of use). CONCLUSION: Women are more susceptible than men to mid-week low mood following weekend use of MDMA; however, both men and women show increased self-rated aggression. These results are interpreted in terms of an attenuation of 5-HT function for a period following acute use of MDMA.     

Mortality in heroin-assisted treatment in Switzerland 1994-2000

BACKGROUND: A major goal of heroin-assisted treatment in Switzerland has been to reduce the drug-related mortality of heroin users. Therefore, a continuous monitoring of deaths under treatment is essential. AIMS: To assess mortality of participants in heroin-assisted treatment in Switzerland over a 7-year period from 1994 to 2000, and to compare this mortality to the general population and to other populations of opioid users, as reported in the literature. METHOD: Estimation of person years under heroin-assisted treatment from the complete case registry of heroin-assisted treatment in Switzerland. Estimation of standardized mortality ratios comparing the population in treatment to the Swiss population (standardized to the year 2000). RESULTS: Over the 7-year period, the crude death rate of patients in heroin-assisted treatment, and including one month after discharge from treatment, was 1% per year. The standardized mortality ratio for the entire observation period was 9.7 (95% C.I. 7.3-12.8), with females having higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was no clear time trend. CONCLUSION: Mortality in heroin-assisted treatment was low compared to the mortality rate of Swiss opioid users 1990s (estimated to be between 2.5 and 3%). It was also low compared to mortality rates of opioid users in other maintenance treatments in other countries as reported in the literature. The SMR was also lower than that reported in the only meta-analysis in the literature: 13.2 (95% C.I. 12.3-14.1). The low mortality rate is all the more noteworthy as heroin-assisted treatment in Switzerland included only refractory opioid addicts with existing severe somatic and/or mental problems. DECLARATION OF INTEREST: No conflicts of interest declared.     

Alcohol consumption and blood pressure in a New Zealand community study

The relationship between stated alcohol consumption and blood pressure was investigated in 901 adults who participated in a multiphasic health survey in Milton in May 1981. Subjects taking oral contraceptives or drugs which could lower blood pressure were excluded. Eighty-five percent of men and 52% of women reported taking some alcohol at least once a month. The percentage using alcohol was highest (96%) in men aged 20-29 years. The reported mean weekly intake by users was 171 g for men and 56 g for women. After adjustment for age and body mass index, there was a positive association between alcohol intake and blood pressure for men. The mean systolic and diastolic pressures of male heavy alcohol users (300 g or more alcohol per week) were, respectively, 9.8 and 8.9 mmHg higher than those of male non-drinkers. No relationship between alcohol intake and blood pressure was found in the women.     

Cannabis use in relation to illicit drug use and health problems among opiate misusers in treatment

The study investigated cannabis use among 200 opiate misusers attending out-patient treatment services at two sites. Three groups were classified according to the frequency of their cannabis use in the previous month; 40.5% were non-users, 40% daily users and the remaining 19.5% were classified as occasional users (they had used on between 1 and 29 days in the previous month). Non-users of cannabis had used heroin in the previous month on more occasions than either daily or occasional users (p < 0.001). Non-cannabis users also reported the highest average frequencies of use of alcohol (p < 0.01) and crack cocaine (p < 0.05). In contrast, daily users of cannabis reported more symptoms of anxiety (p < 0.01) and depression (p < 0.01) than either of the other groups. Finally, daily cannabis users were more likely to report dietary problems than either occasional users or non-users of cannabis. While cannabis use is highly prevalent among opiate misusers in treatment, its relationship to treatment outcome is complex and requires greater research scrutiny.     

Mortality and cause of death among 1705 illicit drug users: A 37 year follow up

Introduction and Aims. To examine the overall mortality and causes of deaths of a large cohort of users of illicit drugs in Stockholm over 37 years. Design and Methods. People with substance abuse were identified through records collected by different institutions in Stockholm in 1967. Subjects were followed in registers recording mortality and cause of death and in‐patient care stays until 2003. Results. More than half (n = 860) of the 1705 identified substance abusers died at an average age of 47 years, 25–30 years younger than the general population. The standardised rate ratio (SRR) for mortality was 3.3 among men and 3.5 among women. Incidence of mortality per 1000 person‐years was also increased, but somewhat lower for women. The difference between these two measures is mainly explained by a lower mortality among women in general. In‐patient care stays with both alcohol and drug‐related diagnoses were associated with higher risk of dying among women than men: SRR = 14.5 and SRR = 4.0, respectively. Accidents and suicide were the most common cause of death among the youngest subjects (15–24 years) and cardiovascular diseases and tumours among the oldest (≥55 years). Discussion and Conclusions. Accidents and suicide, especially at a young age, are two common causes of death that might be prevented by increased awareness in medical personnel, along with better treatment and supportive measures.[Stenbacka M, Leifman A, Romelsjö A. Mortality and cause of death among 1705 illicit drug users: A 37 year follow up. Drug Alcohol Rev 2009]