AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a designer opioid with ~80% of morphine's µ-agonist activity. Over a 6-month period, we encountered nine deaths where AH-7921 was involved and detected in blood from the deceased. Shortly after the last death, on August 1 2013, AH-7921 was scheduled as a narcotic and largely disappeared from the illicit market in Sweden. AH-7921 was measured by a selective liquid chromatography-MS-MS method and the concentrations of AH-7921 ranged from 0.03 to 0.99 µg/g blood. Six of our cases had other drugs of abuse on board and most had other medications such as benzodiazepines, antidepressants and analgesics. However, the other medicinal drugs encountered were present in postmortem therapeutic concentrations and unlikely to have contributed to death. In addition to the parent compound, we identified six possible metabolites where two N-demethylated dominated and four mono-hydroxylated were found in trace amounts in the blood. In conclusion, deaths with AH-7921 seem to occur both at low and high concentrations, probably a result of different tolerance to the drug. Hence, it is reasonable to assume that no sharp dividing line exists between lethal and non-lethal concentrations. Further, poly-drug use did not seem to be a major contributing factor for the fatal outcome.
The case reports for 18 driving cases positive for the synthetic cannabinoid substances XLR-11 and/or UR-144 are discussed. Eleven of these cases had drug recognition expert evaluations performed. Slurred speech, lack of convergence and body and eyelid tremors were the most consistently noted interview characteristic. Pulse and blood pressure of the subjects were within the expected range. Most of the drivers contacted demonstrated poor driving; however, their performance on the standardized field sobriety tests yielded inconsistent diagnostic information. All cases were negative for other commonly detected drugs that affect the central nervous system, although one case was additionally positive for other synthetic cannabinoids. Of the studied cases, six were positive for only UR-144, whereas eight contained only XLR-11. Four cases were found to have both.
A randomized intervention study, "Preventive consultations for 20- to 40-year-old young adults", investigated whether preventive consultations with a general practitioner could help young adults with multiple psychosocial and lifestyle problems to change health behavior. To optimize the response rate of questionnaires at 1 year post-intervention, the non-responders were reminded by telephone. The aim of this study was to examine potential selection bias induced by non-response by comparing responder and non-responder populations at baseline, and to examine the impact on outcomes by comparing initial respondents to respondents after telephone reminding.
Non-responders were compared with primary responders using logistic regression models that included socio-demographic factors, health-related factors, and variables related to the intervention study. In order to describe the impact of including responders after telephone reminding on the intervention's effect on different health, resource, and lifestyle outcomes, we compared results in models including and excluding responders after telephone reminding.
Telephone contact raised the response by 10% from 316 (64%) to 364 (74%) among young adults with multiple problems. Being male was the only factor that significantly predicted non-response in the model after adjustment for other variables. The responders after telephone reminding tended to improve health and lifestyle more than the primary responders, but not significantly so. Although the additional responses did not change the estimates of the 1-year effect on health and lifestyle changes, it contributed to increased precision of the results.
Even though the population of primary non-responders had to some degree a different composition than the primary responders, inclusion of responders after telephone reminding did not significantly change the estimates for effect at the 1-year follow-up; however, the additional responses increased the precision of the estimates.
Cites: Health Educ Res. 2012 Oct;27(5):927-4522473217
Cites: Scand J Public Health. 2011 Jul;39(7 Suppl):131-521775371
Cites: BMC Med Res Methodol. 2010;10:9920964861
Cites: BMC Med Res Methodol. 2010;10:2620356408
Cites: Ann Epidemiol. 2007 Sep;17(9):643-5317553702
Cites: Ugeskr Laeger. 2002 Nov 11;164(46):5367-7212469380
Cites: Am J Epidemiol. 2003 Mar 15;157(6):558-6612631547
Cites: Ann Epidemiol. 2004 Jan;14(1):66-7214664782
Cites: Am J Epidemiol. 2004 Jan 1;159(1):94-10114693664
Cites: Control Clin Trials. 2004 Feb;25(1):31-5214980747
To test the hypothesis that obesity is causally associated with deep venous thrombosis (DVT).
A Mendelian randomization design.
The Copenhagen General Population Study and the Copenhagen City Heart Study combined.
Body mass index (BMI) measurements were available for 87, 574 individuals of Danish descent from the adult general population. All subjects completed questionnaires and were genotyped for the FTO rs9939609 variant.
First events of DVT with or without pulmonary embolism (PE).
The results were assessed using Cox regression, instrumental variable analysis and Poisson regression.
Observationally, the risk of DVT increased with increasing BMI (P-trend 60 years and homozygous for Factor V Leiden) was 35% in obese individuals and 18% in normal-weight individuals.
A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity-specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.
Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned. Aims To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.
Nationwide Swedish quasi-experimental, family-based study following cohorts born 1989-1993 (n(total) = 526 167, n(cousins) = 262 267, n(siblings) = 216 424) between the ages of 15 and 21 years.
Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23-7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44-2.03). Similar pattern of effects was found for substance misuse.
There were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.
Cites: Int J Epidemiol. 2005 Oct;34(5):1089-9916087687
Cites: Am J Psychiatry. 2006 Aug;163(8):1397-40316877653
Somatoform dissociation is supposed to be a vital aspect of the general concept of dissociation. The Somatoform Dissociation Questionnaire-20 (SDQ-20) and the brief version SDQ-5 are self-report instruments constructed to identify somatic dissociation.
In the present study, the psychometric qualities of the Swedish version of the SDQ-20 and its brief version, the SDQ-5, were examined among adolescents and young adults. Reliability and concurrent validity were investigated.
A total of 512 adolescents and young adults participated in the study: 461 adolescents from a non-clinical sample and 50 adolescents and young adults from a clinical eating disorder outpatient unit. They completed the self-report instruments the SDQ-20, the SDQ-5 (part of SDQ-20), the Linköping Youth Life Experience Scale (LYLES, a trauma history scale) and the Dissociation Questionnaire-Sweden (Dis-Q-Sweden).
Both internal consistency and test-retest reliability of the Swedish version of SDQ-20 were good in both the non-clinical (a = 0.83) and the clinical groups (a = 0.84); the reliability for the SDQ-5 was, however, lower (non-clinical a = 0.50, clinical a = 0.64). Significant differences were found between the clinical and non-clinical groups on both somatoform and psychoform dissociation. Correlations between the Dis-Q-Sweden, SDQ-20 and SDQ-5 were generally high. The criterion and convergent validity was acceptable for both scales but somewhat better for SDQ-20 than for SDQ-5.
The advantage with both the SDQ-20 and the SDQ-5 is that they are short questionnaires, but the results suggests that SDQ-20 is preferable based on the higher-quality psychometric properties of the SDQ-20.
Preliminary data support the implementation of individual metacognitive therapy (MCT) for depression. Given the focus of MCT on transpersonal processes, we hypothesized that this treatment should translate well to a group format. In this study, the effects and feasibility associated with group MCT for depression are reported.
Eleven patients who were consecutively referred by general practitioners to a specialist psychiatric practice in Norway participated in an open trial of the effects and feasibility associated with group MCT for depression. All of the patients met the DSM-IV criteria for major depressive disorder (MDD) and were monitored in a baseline period before attending 90-min weekly treatment sessions of group MCT for 10 weeks. The primary symptom outcome measure was severity of depression whilst secondary outcome measures included levels of anxiety, rumination and metacognitive beliefs. We also assessed recovery rates and changes in comorbid Axis I and Axis II diagnoses.
Large clinically significant improvements across all measures were detected at post-treatment and these were maintained at follow-up. Based on objectively defined recovery criteria, all patients were classified as recovered at post-treatment and 91% at 6 months follow-up. The intervention was also associated with significant reductions in comorbid diagnoses.
These preliminary data indicate that group MCT in the treatment of depression is effective, well accepted and it extends clinical application of MCT for depression to group formats as a potential cost-effective intervention.
Studies and clinical experience suggest that kidney disease clusters in families, but few population-based studies have been performed. This study investigates risks and causes of ESRD in Norwegians with and without a first-degree relative with ESRD.
On the basis of data from the Norwegian Population Registry, first-degree relatives for most Norwegians were identified. All Norwegians with ESRD (defined as chronic RRT) since 1980 have been registered in the Norwegian Renal Registry. All Norwegians born in Norway who were alive in 1980 and had at least one registered relative were included. For this study, data on ESRD were available through 2009, and individuals without ESRD were censored at December 31, 2009. Data were analyzed in a cohort design, with ESRD in a first-degree relative of the included person as the main explanatory variable. Risks of ESRD and different causes of ESRD were analyzed using Cox regression statistics.
In total, 5,119,134 individuals were included, of whom 8203 individuals developed ESRD during follow-up and 27,046 individuals had a first-degree relative with ESRD. Compared with individuals without a first-degree relative with ESRD, individuals with a first-degree relative with ESRD had a relative risk of ESRD of 7.2 (95% confidence interval, 6.5 to 8.1). Similar analyses showed that relative risk of ESRD caused by nonhereditary causes was 3.7 (95% confidence interval, 3.1 to 4.4), relative risk of ESRD caused by glomerular disease was 5.2 (95% confidence interval, 4.1 to 6.6), relative risk of ESRD caused by interstitial disease was 4.7 (95% confidence interval, 3.1 to 7.3), relative risk of ESRD caused by diabetic nephropathy was 2.6 (95% confidence interval, 1.6 to 4.1), and relative risk of ESRD caused by hypertensive nephrosclerosis was 2.6 (95% confidence interval, 1.6 to 4.1). Relative risk of nonhereditary parenchymal renal disease was 3.8 (95% confidence interval, 3.1 to 4.7).
As expected, ESRD clusters in families. Interestingly, ESRD without known hereditary cause also clusters in families.
Cites: J Am Soc Nephrol. 2005 Jul;16(7):2088-9715930092
Cites: Am J Kidney Dis. 1998 Nov;32(5):794-8019820449
Cites: J Am Soc Nephrol. 2007 Apr;18(4):1344-5217344425
Cites: Clin J Am Soc Nephrol. 2007 Nov;2(6):1306-1617942768
Cites: Nat Genet. 2008 Oct;40(10):1175-8418794856
Cites: J Am Soc Nephrol. 2010 Sep;21(9):1422-620688934
Cites: Kidney Int. 2010 Oct;78(7):698-70420668430
Cites: J Am Soc Nephrol. 2010 Nov;21(11):1819-3420864689
Cites: PLoS Genet. 2011 Jun;7(6):e100215021698141
Cites: J Am Soc Nephrol. 2011 Nov;22(11):2129-3721997394
Cites: N Engl J Med. 2011 Dec 22;365(25):2398-41122187987
The DSM-5 alcohol use disorder (AUD) criteria proposal contains 11 criteria that include most of the DSM-IV abuse and dependence criteria plus craving. The aims of the current study in a large and international alcohol-consuming sample were to confirm the dimensionality of the DSM-5 AUD criteria and to differentiate grades of severity of DSM-5 AUD in subjects who pass the proposed DSM-5 diagnostic threshold of two criteria.
We used the World Health Organization (WHO)/International Society on Biomedical Research on Alcoholism (ISBRA) Study on State and Trait Markers of Alcohol Use and Dependence dataset. Subjects included in the analyses were aged = 18 years and were recruited in five countries: Australia, Brazil, Canada, Finland and Japan. Assessment of AUD and additional characteristics was conducted using an adapted version of the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS). Dimensionality of the DSM-5 criteria was evaluated using factor analysis and item response theory (IRT) models. The IRT results led to the classification of AUD patients into three severity groups. External validators were used to differentiate statistically across subgroups.
A total of 1424 currently drinking individuals were included in the analyses. Factor and IRT analyses confirmed the dimensional structure of DSM-5 AUD criteria. More than 99% of the subjects could be allocated to one of the suggested severity subgroups. The magnitude of the external validators differed significantly across the severity groups.
The results confirm the dimensional structure of the proposed DSM-5 AUD criteria. The suggested stages of severity (mild, moderate and severe) may be useful to clinicians by grouping individuals not only in the mild but also in the moderate to severe spectrum of DSM-5 AUD.
Greater force produced with eccentric (ECC) compared to concentric (CONC) contractions, may comprise a stronger driver of muscle growth, which may be further augmented by protein supplementation. We investigated the effect of differentiated contraction mode with either whey protein hydrolysate and carbohydrate (WPH + CHO) or isocaloric carbohydrate (CHO) supplementation on regulation of anabolic signalling, muscle protein synthesis (MPS) and muscle hypertrophy. Twenty-four human participants performed unilateral isolated maximal ECC versus CONC contractions during exercise habituation, single-bout exercise and 12 weeks of training combined with WPH + CHO or CHO supplements. In the exercise-habituated state, p-mTOR, p-p70S6K, p-rpS6 increased by approximately 42, 206 and 213 %, respectively, at 1 h post-exercise, with resistance exercise per se; whereas, the phosphorylation was exclusively maintained with ECC at 3 and 5 h post-exercise. This acute anabolic signalling response did not differ between the isocaloric supplement types, neither did protein fractional synthesis rate differ between interventions. Twelve weeks of ECC as well as CONC resistance training augmented hypertrophy with WPH + CHO group compared to the CHO group (7.3 ± 1.0 versus 3.4 ± 0.8 %), independently of exercise contraction type. Training did not produce major changes in basal levels of Akt-mTOR pathway components. In conclusion, maximal ECC contraction mode may constitute a superior driver of acute anabolic signalling that may not be mirrored in the muscle protein synthesis rate. Furthermore, with prolonged high-volume resistance training, contraction mode seems less influential on the magnitude of muscle hypertrophy, whereas protein and carbohydrate supplementation augments muscle hypertrophy as compared to isocaloric carbohydrate supplementation .