SARS-CoV-2 variant with mutations in N gene affecting detection by widely used PCR primers.

While most of the spontaneous mutations in the viral genome have no functional, diagnostic, or clinical consequences, some have. In February 2021, we noticed in Southern Finland coronavirus disease 2019 cases where two commercial polymerase chain reaction (PCR) analyses failed to recognize the used N gene target but recognized the other target gene of severe acute respiratory syndrome coronavirus 2. Complete viral genome sequence analysis of the strains revealed several mutations that were not found at that time in public databases. A short 3 bp deletion and three subsequent single nucleotide polymorphisms in the N gene were found exactly at the site where an early published and widely used N gene-based PCR primer is located, explaining the negative results in the N gene PCR. Later the variant strain was identified as a member of the B.1.1.318 Pango lineage that had first been found from Nigerian samples collected in January 2021. This strain shares with the Beta variant the S gene E484K mutation linked to impaired vaccine protection, but differs from this variant in several other ways, for example by deletions in the N gene region. Mutations in the N gene causing diagnostic resistance and on the other hand E484K mutation in the causing altered infectivity warrants careful inspection on virus variants that might get underdiagnosed.

The effect of banning MDPV on the incidence of MDPV-positive findings among users of illegal drugs and on court decisions in traffic cases in Finland.

In this study, we sought to determine what impact the banning of 3, 4- methylenedioxypyrovalerone (MDPV) had on the incidence of MDPV-positive findings and on user profiles in driving under the influence of drugs (DUID) and postmortem (PM) investigations in Finland. All MDPV-positive cases and a selection of corresponding court cases between 2009 and 2012 were examined. The median serum concentration of MDPV in DUID cases was 0.030 mg/L and in PM blood 0.12 mg/L. The number of MDPV-positive cases decreased both in DUID and PM investigations after the drug was banned. The decrease in the mean monthly numbers of MDPV-positive DUID cases was 51.1%. In court cases, MDPV was rarely mentioned until banned and frequently mentioned thereafter. Of the convicted, 37% were without a fixed abode, 98% had other charges besides that of DUID, and 13% appeared in the study material more than once. In MDPV-positive PM cases, the proportion of suicides was very high (24%). Research on new psychoactive substances is required not only to support banning decisions but more importantly to be able to provide a scientific assessment of the risks of these new substances to the public and potential users.

Sedative-hypnotics are widely abused by drivers apprehended for driving under the influence of drugs.

BACKGROUND: Sedative-hypnotics are commonly encountered in drivers apprehended for driving under the influence of drugs (DUID). Previous research has mainly concentrated on the residual effects of the drugs. METHODS: In this study, the extent of sleep medication use and abuse among drivers apprehended on suspicion of DUID was assessed. Additionally, the prevalence and concentrations of the drugs, concomitant use of other drugs of abuse, and the age and sex of the drivers positive for the most commonly prescribed sedative-hypnotics (temazepam, midazolam, nitrazepam, zopiclone, and zolpidem) in DUID cases in Finland in 2009 to 2011 were examined. RESULTS: Sedative-hypnotics were found in 3155 samples of the 13,248 that were analyzed. Temazepam was present in over half of the cases (57.9%), along with other benzodiazepines such as midazolam (13.1%) and nitrazepam (7.0%) and the non-benzodiazepine hypnotics zopiclone (12.2%) and zolpidem (9.8%). The mean age of the drivers using the studied sedative-hypnotics was 33.5 years. Many of the drivers were polydrug users; concomitant stimulant use was found in nearly half of the cases. Cannabis and alcohol were also very common co-findings. In nearly 20% of the cases, the driver had taken more than 1 of the studied sedative-hypnotics; only 2.5% had no findings other than a single sedative-hypnotic in their blood. The drug use pattern of those positive for zopiclone and zolpidem was somewhat different from that of users of benzodiazepine sedative-hypnotics; their age was higher and the concomitant use of illegal stimulants was markedly less prevalent than among the users of temazepam, midazolam, and nitrazepam. CONCLUSIONS: There were very few cases in our study population where the positive sedative-hypnotic finding could have been due to appropriate medical use. The extremely prevalent concomitant use of other psychoactive drugs and the high median serum concentrations of the studied sedative-hypnotics suggest their widespread abuse among apprehended drivers.

Pregabalin serum levels in apprehended drivers.

Pregabalin is a medicinal drug used mainly for the treatment of epilepsy and neuropathic pain. It has been shown to possess an abuse potential and in recent years some reports of illegal use have been published. In order to further evaluate the extent and nature of pregabalin abuse, serum pregabalin levels of drivers apprehended for driving under the influence of drugs (DUID) in Finland in 2012 were assessed. The samples were analysed by an LC-MS/MS system and the results were evaluated in relation to the typical therapeutic range of pregabalin as well as the age and gender of the driver. Pregabalin was detected in 206 samples in the study period. The median (range) serum concentration was 6.2 (0.68-111.6)mg/L. In nearly 50% of the cases the serum concentration was above the typical therapeutic range. In most of the cases the driver had also taken other drugs besides pregabalin, the mean number of concomitantly taken drugs being four. Our data indicate that pregabalin is being used at high doses, probably for recreational purposes. The vast majority of the drivers positive for pregabalin in our study material had used pregabalin as a part of a spectrum of psycho-active drugs and thus qualified as probable drug abusers. In these cases pregabalin probably contributed to their driving impairment but to what extent remained unclear in this study.

Comparison of breath-alcohol screening test results with venous blood alcohol concentration in suspected drunken drivers.

Hand-held electronic breath-alcohol analyzers are widely used by police authorities in their efforts to detect drunken drivers and to improve road-traffic safety. Over a three month period, the results of roadside breath-alcohol tests of drivers apprehended in Finland were compared with venous blood alcohol concentration (BAC). The mean (median) time between sampling blood and breath was 0.71h (0.58h) with a range from 0 to 6h. Some hand-held instruments gave results as the concentration of alcohol in breath and were converted into BAC assuming a blood-breath alcohol ratio (BBR) of 2260. The mean venous BAC (1.82g/kg) in traffic offenders was higher than the result predicted by the hand-held breath analyzers (1.72g/kg). In 1875 roadside tests, the relationship between venous BAC (x) and BrAC (y) was defined by the regression equation y=0.18+0.85x. The coefficients show both a constant bias (y-intercept 0.18g/kg) and a proportional bias (slope=0.85). The residual standard deviation (SD), an indicator of random variation, was ±0.40g/kg. After BAC results were corrected for the time elapsed between sampling blood and breath, the y-intercept decreased to 0.10g/kg and 0.004g/kg, respectively, when low (0.1g/kg/h) and high (0.25g/kg/h) rates of alcohol elimination were used. The proportional bias of 0.85 shows that the breath-alcohol test result reads lower than the actual BAC by 15% on average. This suggests that the BBR of 2260 used for calibration should be increased by about 15% to give closer agreement between BAC and BrAC. Because of the large random variation (SD±0.40g/kg), there is considerable uncertainty if and when results from the roadside screening test are used to estimate venous BAC. The roadside breath-alcohol screening instruments worked well for the purpose of selecting drivers above the statutory limit of 0.50g/kg.

Prevalence and blood concentrations of desoxypipradrol (2-DPMP) in drivers suspected of driving under the influence of drugs and in post-mortem cases.

The aim of this study was to assess the incidence of the use of desoxypipradrol (2-DPMP) among drivers apprehended on suspicion of driving under the influence of drugs (DUID) and the prevalence of the drug in post-mortem cases in Finland. Serum samples from drivers apprehended on suspicion of DUID and blood samples from post-mortem cases in Finland between October 2010 and May 2012 were analysed for the presence of desoxypipradrol. All samples were analysed for desoxypipradrol by mass spectrometric methods following comprehensive drug screening. Psychomotor performance of subjects was assessed by a clinician. There were 106 positive desoxypipradrol samples from apprehended drivers (1.7% of all confirmed DUID cases) in the study period. In most cases amphetamine and/or benzodiazepines were also present. The median (range) desoxypipradrol concentration was 0.073 mg/L (0.006-0.890 mg/L). The presence of other psychoactive drugs confounded assessment of the effect of desoxypipradrol on psychomotor performance except for one case in which it was the only drug present at pharmacologically active levels. Desoxypipradrol was found in 5 autopsy cases (0.05% of the investigated cases) and thought to contribute to death in two of these. Even though there are few data available on the pharmacology of desoxypipradrol, based on our findings, and the growing number of users, it is reasonable to assume that desoxypipradrol - a long-acting psychostimulant with dangerous side effects has an increasing detrimental impact on traffic safety in Finland. However, it was only rarely found to be the cause of death in post-mortem cases.

Phenazepam abuse in Finland: findings from apprehended drivers, post-mortem cases and police confiscations.

Phenazepam is a long-acting benzodiazepine that, unlike other benzodiazepines, is currently not scheduled as a narcotic in Finland, most other European countries or the USA. It is used as an anxiolytic, sedative-hypnotic and anti-epileptic, mainly in Russia. In Finland, as well as in some other countries, an increase in the unauthorized use of phenazepam has been observed in recent years. In the one year period between July 1, 2010 and June 30, 2011 the prevalence of phenazepam in Finland was assessed among drivers apprehended for driving under the influence of drugs (DUID), in medico-legal autopsy cases and in police confiscations of illicit drugs. In DUID cases an LC-MS/MS method preceded by solid phase extraction was used for the determination of phenazepam. In the post-mortem investigations the sample preparation consisted of liquid-liquid extraction followed by derivatization and the determination was carried out by GC-MS. The police confiscations were analysed by GC-MS. There were 141 positive phenazepam cases among apprehended drivers, representing approximately 3.5% of all confirmed drug cases (n=4007) in this time period. The median (range) phenazepam blood concentration in DUID cases was 0.061 mg/L (0.004-3.600 mg/L). The median phenazepam concentration in cases with no concomitant stimulant use was significantly higher than the overall median concentration. Phenazepam was found in 17 medico-legal autopsy cases and the median (range) blood concentration was 0.048 mg/L (0.007-1.600 mg/L). Phenazepam was not considered by the medico-legal team to be the sole cause of death in any of the cases, the majority of them being accidental opiod overdoses. There were 26 seizures of phenazepam by the Police in the time period studied, some of the batches consisted of a mixture of phenazepam and stimulant designer drugs. The data show that phenazepam abuse is a widespread phenomenon in Finland. A typical user was a male multi-drug user in his 30s. The concentration range of phenazepam among apprehended drivers and medico-legal autopsy cases was wide and the drug was usually found along with other psychoactive drugs. Therefore, although it seems likely that phenazepam contributed to impairment of driving in some DUID cases, the extent of its effect remains unclear and further studies are needed to define the concentrations causing impairment and toxicity.

Randomized trial of the efficacy of bright-light exposure and aerobic exercise on depressive symptoms and serum lipids.

BACKGROUND: Season-related subsyndromal depressive symptoms during winter are common among populations at high latitudes. Both physical exercise and exposure to bright light can relieve the fatigue and downturn of mood associated with the shortening length of day. Serum cholesterol level may be related to changes in mood, but the evidence is contradictory. Our objective was to compare the effect of aerobic exercise with or without bright-light exposure on health-related quality of life, mood, and serum lipids in a sample of relatively healthy adult subjects. METHOD: A randomized controlled trial was conducted with subjects allocated to group aerobics training in a gym with bright light (2500-4000 lux) (N = 40) or normal illumination (N = 42) or to relaxation/stretching sessions in bright light as a control group (N = 42) twice a week for a period of 8 weeks. Changes in mood were recorded using questionnaires at the beginning of the study, at weeks 4 and 8. and at follow-up 4 months after the study. A blood sample was drawn before and after the 8-week intervention to measure the concentrations of serum lipids. RESULTS: Ninety-eight subjects completed the 8-week study. Both exercise and bright light effectively relieved depressive symptoms. Bright light reduced atypical depressive symptoms more than exercise (p = .03), based on the atypical symptoms subscore of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version Self-Rating Format. There were no significant differences between the study groups in the changes in serum lipid levels. CONCLUSION: Bright light administered twice a week, alone or combined with physical exercise, seems to be a useful intervention for relieving seasonal mood slumps.