The "Clubs against Drugs" program in Stockholm, Sweden: two cross-sectional surveys examining drug use among staff at licensed premises

<p>Abstract</p> <p>Background</p> <p>The objective of this study is to examine self-reported drug use among staff at licensed premises, types of drugs used, attitudes towards drugs, and observed drug use among guests. Results are presented from two measurement points (in 2001 and 2007/08). This study was carried out within the framework of the "Clubs against Drugs" program, which is a community-based multi-component intervention targeting licensed premises in Stockholm, Sweden.</p> <p>Methods</p> <p>Two cross-sectional surveys were conducted, the first in 2001 and the second in 2007/08. Staff at licensed premises attending server training were asked to participate in the anonymous survey. A survey was administered in a classroom setting and consisted of four sections: 1) demographics, 2) respondents' own drug use experience, 3) respondents' attitudes towards drug use, and 4) observed drug use among guests at licensed premises.</p> <p>Results</p> <p>Data were collected from 446 staff in 2001 and 677 staff in 2007/08. The four most commonly used drugs among staff were cannabis, cocaine, amphetamine, and ecstasy. The highest rates of drug use were reported by staff in the two youngest age groups, i.e., those younger than 25 and those between the ages of 25 and 29. In 2007/08 staff reported significantly lower rates of drug use than staff in 2001. Last year drug use for the sample in 2007/08 was 19% compared to 27% for the 2001 sample. While drug-using staff compared to non drug-using staff reported more observations of drug use among guests, they were less inclined to intervene. Overall, staff reported restrictive attitudes towards drugs.</p> <p>Conclusions</p> <p>The prevalence of life-time and last year drug use among staff at licensed premises is high compared to the general population in Sweden. Lower rates of self-reported drug use among staff were reported in 2007/08. The results of this study highlight that staff at licensed premises represent an important target population in club drug prevention programs.</p

Measuring substance use in the club setting: a feasibility study using biochemical markers

<p>Abstract</p> <p>Background</p> <p>During the last few decades the use of club drugs (e.g., cocaine, amphetamines) has been of increased concern in nightlife settings. Traditionally, surveys have been used to estimate the use of club drugs, however, they mostly rely on self-reports which may not be accurate. Recent advances have allowed for readily accessible drug testing methods such as oral fluid drug testing. Nevertheless, research using oral fluid sampling to measure the frequency of drug use in the club environment is scarce. The objective of this study is to evaluate the feasibility of measuring the frequency of alcohol and drug use among Swedish clubbers using breath alcohol and oral fluid drug testing.</p> <p>Method</p> <p>The setting was a 40 hour electronic music dance event (EMDE) on a cruise ship on the Baltic Sea, departing from Sweden, with 875 passengers. Groups of participants at the EMDE were randomly invited to participate. Data were collected with face-to-face and self-administered questionnaires. Further, oral fluid samples were collected to determine illicit drug use, and blood alcohol concentration (BAC) levels were measured using a breath analyzer.</p> <p>Results</p> <p>A total of 422 passengers were asked to participate in the study whereof 21 declined (5.0% refusal rate). Of the 401 study participants (accounting for 45.8% of all attendees), 5 declined oral fluid drug testing. Results show that there was a discrepancy between self-reported and actual drug use as 10.1% of the participants were positive on illicit drug use (amphetamines, ecstasy/MDMA, cannabis, cocaine), while only 3.7% of the participants reported drug use during the last 48 hours. The average BAC level was 0.10% and 23.7% had BAC levels ≥ 0.15%, while 5.9% had levels below the detection limit. The mean BAC levels for the illicit drug users were significantly higher (<it>p </it>= 0.004) than for non-drug users (0.13% vs. 0.10%). Self-reported AUDIT-C scores (using a threshold of ≥ 5 for men and ≥ 4 for women) revealed that 76.0% of the men and 80.7% of the women had risky alcohol consumption patterns.</p> <p>Conclusion</p> <p>This study indicates that it is feasible to conduct breath alcohol and oral fluid drug testing in a Swedish club setting.</p

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of <it>RAI </it>IVS1 A4364G^A, <it>ERCC1 </it>Asn118Asn^Tand <it>ASE-1 </it>G-21A^G. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.</p> <p>Methods</p> <p>Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.</p> <p>Results</p> <p>No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.</p> <p>Conclusion</p> <p>Our results suggest that the <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.</p

Origin of micro-scale heterogeneity in polymerisation of photo-activated resin composites

Photo-activated resin composites are widely used in industry and medicine. Despite extensive chemical characterisation, the micro-scale pattern of resin matrix reactive group conversion between filler particles is not fully understood. Using an advanced synchrotron-based wide-field IR imaging system and state-of-the-art Mie scattering corrections, we observe how the presence of monodispersed silica filler particles in a methacrylate based resin reduces local conversion and chemical bond strain in the polymer phase. Here we show that heterogeneity originates from a lower converted and reduced bond strain boundary layer encapsulating each particle, whilst at larger inter-particulate distances light attenuation and monomer mobility predominantly influence conversion. Increased conversion corresponds to greater bond strain, however, strain generation appears sensitive to differences in conversion rate and implies subtle distinctions in the final polymer structure. We expect these findings to inform current predictive models of mechanical behaviour in polymer-composite materials, particularly at the resin-filler interface

Admixture mapping: from paradigms of race and ethnicity to population history

Admixture mapping is a whole genome association strategy that takes advantage of population history—or genetic ancestry—to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research—their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders

Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study

BACKGROUND: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. METHODS: We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg(194)Trp, Arg(280)His, Arg(399)Gln, XRCC3 Thr(241)Met and XPD Lys(751)Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. RESULTS: The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas. CONCLUSION: Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg(280)His polymorphism and a reduced risk associated with the XRCC1 Arg(399)Gln polymorphism. Interestingly, individuals with the XPD Lys(751)Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas

Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: implications for calcification-related chronic inflammatory diseases

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and gamma-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein gamma-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNF alpha, IL-1 beta and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application.Portuguese Science and Technology Foundation (FCT) [PTDC/SAU-ORG/117266/2010, PTDC/BIM-MEC/1168/2012, UID/Multi/ 04326/2013]; FCT fellowships [SFRH/BPD/70277/2010, SFRH/BD/111824/2015

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise

Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645–1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second author’s name was presented incorrectly. The author’s name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel

Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension

BACKGROUND: Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. METHODS AND RESULTS: Four hundred seventy‐seven patients with mild‐to‐moderate Alzheimer disease were randomized to the calcium‐channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop ≥20/≥10 mm Hg after 1 minute of standing) and OH‐related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow‐up visits. Mean age of the study population was 72.2±8.2 years and mean Mini‐Mental State Examination score was 20.4±3.8. Baseline blood pressure was 137.8±14.0/77.0±8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by −7.8/−3.9 mm Hg for nilvadipine and by −0.4/−0.8 mm Hg for placebo (P<0.001). Across the 78‐week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI]=1.1 [0.8–1.5], P=0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7±13.8% versus 7.3±11.6%). OH‐related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. CONCLUSIONS: This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild‐to‐moderate Alzheimer disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340

Developing the practice context to enable more effective pain management with older people: an action research approach

Background\ud \ud This paper, which draws upon an Emancipatory Action Research (EAR) approach, unearths how the complexities of context influence the realities of nursing practice. While the intention of the project was to identify and change factors in the practice context that inhibit effective person-centred pain management practices with older people (65 years or older), reflective critical engagement with the findings identified that enhancing pain management practices with older people was dependent on cultural change in the unit as a whole. \ud \ud Methods\ud \ud An EAR approach was utilised. The project was undertaken in a surgical unit that conducted complex abdominal surgery. Eighty-five percent (n = 48) of nursing staff participated in the two-year project (05/NIR02/107). Data were obtained through the use of facilitated critical reflection with nursing staff. \ud \ud Results\ud \ud Three key themes (psychological safety, leadership, oppression) and four subthemes (power, horizontal violence, distorted perceptions, autonomy) were found to influence the way in which effective nursing practice was realised. Within the theme of 'context,' effective leadership and the creation of a psychologically safe environment were key elements in the enhancement of all aspects of nursing practice. \ud \ud Conclusions\ud \ud Whilst other research has identified the importance of 'practice context' and models and frameworks are emerging to address this issue, the theme of 'psychological safety' has been given little attention in the knowledge translation/implementation literature. Within the principles of EAR, facilitated reflective sessions were found to create 'psychologically safe spaces' that supported practitioners to develop effective person-centred nursing practices in complex clinical environments