Occupational health physicians as users of electronic health records.

BACKGROUND: Electronic health records (EHRs)' purpose is to facilitate the documentation of patient data and to improve the exchange of information between the professionals involved in a patient's care. AIMS: To investigate occupational health (OH) physicians' experiences of EHRs and the factors hampering work. METHODS: An electronic questionnaire was sent to physicians working in OH services in April 2017 and a total of 342 OH physicians participated in the study. The results were reported as quantities and percentages. The survey text was analysed using data-driven content analysis. RESULTS: The respondents considered their EHR stable in terms of technical features but the routine tasks with EHR were not straightforward. Also, the documentation of patient data for statistical purposes took an unreasonable amount of time and the access to patient data from other organizations was poor. Instead, a well-functioning feature of EHRs were electronic prescriptions. The factors, which hampered respondents' work, were constant or frequent time pressure, too little time to do their job properly and a stress caused by uncompleted tasks. CONCLUSIONS: This study showed that the usability problems of EHRs were the slowness, unexpected downtimes and difficulties in obtaining patient data. Also, respondents felt very often a lack of time in their work. OH physicians' work is best supported by EHRs that consider their specific role in healthcare, i.e. the assessment of work ability, the co-ordination of care and rehabilitation and support for return to work.

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Legislation of direct-to-consumer genetic testing in Europe: a fragmented regulatory landscape.

Despite the increasing availability of direct-to-consumer (DTC) genetic testing, it is currently unclear how such services are regulated in Europe, due to the lack of EU or national legislation specifically addressing this issue. In this article, we provide an overview of laws that could potentially impact the regulation of DTC genetic testing in 26 European countries, namely Austria, Belgium, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, the Netherlands and the United Kingdom. Emphasis is placed on provisions relating to medical supervision, genetic counselling and informed consent. Our results indicate that currently there is a wide spectrum of laws regarding genetic testing in Europe. There are countries (e.g. France and Germany) which essentially ban DTC genetic testing, while in others (e.g. Luxembourg and Poland) DTC genetic testing may only be restricted by general laws, usually regarding health care services and patients' rights.

Recent developments in genetics and medically-assisted reproduction: from research to clinical applications†‡.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Patenting and licensing in genetic testing: recommendations of the European Society of Human Genetics.

Patents for inventions can be beneficial for society, if they drive innovation and promote progress. In most areas, the patenting system works satisfactorily. However, it must be recognized that in some instances it can also be problematic; this is the case in the field of genetics, and particularly in the area of genetic testing. As patents should serve their original purpose (promoting innovation through a fair reward system for the inventors), the European Society of Human Genetics (ESHG) suggests ways to improve the mechanisms that already form part of the patents system as a whole. In brief, the ESHG recommends limiting the breadth of the claims in genetic patents and, more practically, to reduce the number of patents by limiting the patentable subject matter, thereby improving the quality of the patents that will eventually be granted. There is also a suggestion to redefine the concept of utility in patent law, by taking account of downstream clinical experience. The ESHG sees no harm in the patenting of novel technical tools for genetic testing (eg PCR or chip technologies), as they can promote investment and still allow for invention around them. Many disputes between supporters of the patenting system and the public revolve around ethical issues. The European Patent Office should consider the benefit of having an ethics committee to consider issues of major interest, such as patents applied to genes. The problem of licensing should also be addressed. Practically, this means supporting the Organisation for Economic Co-operation and Development guidelines, which prescribe that licences should be non-exclusive and easily obtainable, both in practical and in financial terms. To promote this, the practical exploration of alternative models for licensing, like patent pools and clearinghouses, is a prerequisite. To better track developments in this field, the establishment of a voluntary reporting system, whereby geneticists could report on any issues related to new and/or old patents or licences in the light of service provision to patients, would be worthwhile. Finally, the ESHG is calling upon all stakeholders to start the process of developing a code of conduct for partners with patents, covering ethical aspects as well as smooth licensing arrangements.

Patenting and licensing in genetic testing.

Patents for inventions can be beneficial for society, if they drive innovation and promote progress. In most areas, the patenting system works satisfactorily. However, it must be recognized that in some instances it can also be problematic; this is the case in the field of genetics, and particularly in the area of genetic testing. As patents should serve their original purpose (promoting innovation through a fair reward system for the inventors), the European Society of Human Genetics (ESHG) suggests ways to improve the mechanisms that already form part of the patents system as a whole. In brief, the ESHG recommends limiting the breadth of the claims in genetic patents and, more practically, to reduce the number of patents by limiting the patentable subject matter, thereby improving the quality of the patents that will eventually be granted. There is also a suggestion to redefine the concept of utility in patent law, by taking account of downstream clinical experience. The ESHG sees no harm in the patenting of novel technical tools for genetic testing (eg PCR or chip technologies), as they can promote investment and still allow for invention around them. Many disputes between supporters of the patenting system and the public revolve around ethical issues. The European Patent Office should consider the benefit of having an ethics committee to consider issues of major interest, such as patents applied to genes. The problem of licensing should also be addressed. Practically, this means supporting the Organisation for Economic Co-operation and Development guidelines, which prescribe that licenses should be non-exclusive and easily obtainable, both in practical and in financial terms. To promote this, the practical exploration of alternative models for licensing, like patent pools and clearinghouses, is a prerequisite. To better track developments in this field, the establishment of a voluntary reporting system, whereby geneticists could report on any issues related to new and/or old patents or licenses in the light of service provision to patients, would be worthwhile. Finally, the ESHG is calling upon all stakeholders to start the process of developing a code of conduct for partners with patents, covering ethical aspects as well as smooth licensing arrangements.

Preimplantation genetic diagnosis (PGD) in Europe: diversity of legislation a challenge to the community and its citizens.

Preimplantation genetic diagnosis (PGD) aims to safeguard the reproductive confidence of couples who have an increased risk of having a child with a serious hereditary disease. Non-directive genetic counselling is an essential part of PGD. Lately, performance of PGD for some new and non-medical indications, such as selecting for a tissue-matching embryo for a saviour sibling, or sex-selection for family-balancing, has raised ethical concerns. Who decides when to perform PGD, and for which conditions? The European member states have very diverse regulation on PGD. Some countries totally ban PGD, while the others keep close track of the new applications. The people in need of PGD seek it in the other member states. These cross-border treatments cause psychological stress and pose many so far unresolved legal questions. The individuals need more information about all the aspects of PGD. This article analyses contemporary indications for PGD in Europe and relevant ethical discussion, and second, shows the diversity in regulation and reflects the consequences thereof.

Effects of fluid-flow velocity and water quality on planktonic and sessile microbial growth in water hydraulic system.

Water hydraulic systems use water instead of oil as a pressure medium. Microbial growth in the system may restrict the applicability this technology. The effects of fluid-flow velocity and water quality on microbial growth and biofilm formation were studied with a pilot-scale water hydraulic system. The fluid-flow velocities were 1.5-5.2 m/s and the corresponding shear stresses 9.1-84 N/m2. The fluid-flow velocity had an insignificant effect on the total bacterial numbers and the numbers of viable heterotrophic bacteria in the pressure medium. Microbial attachment occurred under high shear stresses. The fluid-flow velocity did not affect the biofilm formation in the tank. Increase in the flow velocity decreased the bacterial densities on the pipe surfaces indicating preferable biofilm formation on areas with low flow velocity. Using ultrapure water as the pressure medium decreased the total cell numbers and resulted in slower growth of bacteria in the pressure medium. Lowering the nutrient concentration retarded biofilm formation but did not affect the final cell densities. The decreasing pressure medium nutrient concentration favoured microbial attachment in the tank instead of the pipelines. In conclusion, microbial growth and biofilm formation in water hydraulic systems cannot be controlled by the fluid-flow velocity or the quality of the pressure medium.

Effects of high and fluctuating pressure on microbial abundance and activity in a water hydraulic system.

The effects of high and fluctuating pressure up to 220 bar on microbial growth and activity were determined in a pilot-scale water hydraulic system. An increase in the pipeline pressure from 70 to 220 bar decreased the total and the viable cell number in the pressure medium from 2.2(+/-0.5)x10(5) to 4.9(+/-1.5)x10(4) cells/ml and from 5.7(+/-2.8)x10(4) to 1.3(+/-0.7)x10(4) cfu/ml, respectively. Microbial attachment in the non-pressurised tank of the hydraulic system increased with increasing pipeline pressure [from 1.0(+/-0.3) to 3.8(+/-2.7)x10(5) cells/cm(2) on stainless steel]. The phosphatase, aminopeptidase and beta-glucosidase activities in the pressurised medium were between 0.02 and 1.4 micromol/lh ( V(max)) and decreased in response to increasing pipeline pressure. The alpha-glucosidase activity was detected only at 70 bar and the glucuronidase activity only occasionally. Based on principal component and cluster analyses, both the pressure applied and the original filling water quality affected substrate utilisation patterns. This study demonstrated the capability of freshwater bacteria to tolerate high and fluctuating pressure in a technical water system. Microbial survival was due to attachment and growth on the surfaces of the non-pressurised components and the nutrient flux released by cell lysis in the pressurised components. In summary, high pressures in water hydraulic systems do not prevent potential microbiologically related operational problems.

Cation modulation of GABA(A) receptors in brain sections of AT and ANT rats.

Changes in magnesium ion (Mg(2+)) concentration may be implicated in alcohol-related behaviors through modulation of neuronal excitability by actions on ligand-gated ion channels. To study whether putative Mg(2+)-binding sites differ between two rat lines, alcohol-insensitive (AT) and alcohol-sensitive (ANT) rats, selectively outbred for differential sensitivity to the motor-impairing effect of ethanol, we compared the effect of Mg(2+) on [35S]tert-butylbicyclophosphorothionate ([35S]TBPS) binding to GABA(A) receptors with the use of ligand autoradiographic analyses of brain sections from these rats. There were some slight differences between the rat lines in modulation of the binding in the forebrain. A low concentration of Mg(2+) (0.1 mM) inhibited basal [35S]TBPS binding more efficiently in the central gray matter and hippocampus in the ANT rats than in the AT rats. In the presence of gamma-aminobutyric acid, the effect of a low concentration of Mg(2+) was higher in the caudate-putamen and inner layer of the cerebral cortex in the AT rats than in the ANT rats. No difference between the rat lines was found at a higher (3 mM) Mg(2+) concentration. Furosemide, a GABA(A) antagonist selective for cerebellar granule cell-specific alpha6beta2/3 subunit-containing receptors, was less efficient in antagonizing the Mg(2+)-induced inhibition of [35S]TBPS binding in the ANT rats than in the AT rats. Another divalent cation, zinc ion, was less efficient in displacing [35S]TBPS binding from the cerebellar granule cell layer in the ANT rats than in the AT rats, whereas a trivalent cation, lanthanum ion, produced identical modulation of the binding in the two rat lines. The results indicate that the alcohol-sensitive ANT rats have altered cerebellar granule cell--specific alpha6 subunit--containing GABA(A) receptors and seem to indicate that these receptors might be implicated in the sensitivity difference of the rat lines to ethanol and sedative drugs.

Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers.

A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors. We now report that the effects of urocanic acid on binding of a convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in brain membrane homogenates are dependent on pH of the incubation medium, the agonistic actions being enhanced at the normal pH of the skin (5.5). Using Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A) receptors, the low pH potentiated the direct agonistic action of trans-urocanic acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences between urocanic acid isomers in functional activity at one putative receptor site of immunosuppression, the GABA(A) receptor, the presence of which in the skin remains to be demonstrated.

Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking.

Effects of a continuous naloxone infusion via osmotic pumps on alcohol drinking and opioid receptor density and function in the high-drinking AA (Alko, Alcohol) rats were examined. AA rats were trained to drink 10% (v/v) ethanol in a 1-h limited access procedure and implanted with subcutaneous osmotic pumps delivering either saline, a low dose (0.3 mg/kg per hour), or a high dose (3.0 mg/kg per hour) of naloxone for 7 days. The pumps were then removed and alcohol, food and water intakes were measured for another 4 days. Compared with saline, both naloxone doses significantly suppressed 1-h alcohol intake during the 7-day infusion. The suppression was smaller than that by a bolus injection of the same daily dose 15 min before the session, although a complete blockade of morphine-induced antinociception was achieved even with the smaller naloxone infusion. Significant decreases were also seen in daily food and water intake during the first days, but they quickly returned to their previous baselines. After pump removal, rats of both naloxone-treated groups rapidly increased their alcohol drinking and reached the pretreatment baseline, while their food and water intakes significantly surpassed their baselines. Naloxone infusion at 3.0 mg/kg per hour for 7 days significantly decreased 24-h alcohol drinking without affecting alcohol preference. Twenty-four hours after pump removal, autoradiography with [3H]DAMGO, [3H]DPDPE and [3H]U-69,543 revealed an up-regulation of mu-, delta- and kappa-opioid receptor binding sites in many brain areas of these animals. This receptor up-regulation was functional, because receptor coupling to G-protein activation was enhanced by agonist ligands, as revealed by [35S]GTPgammaS autoradiography. A good correlation existed between ligand binding densities and G-protein activation for mu- and kappa-receptors in control and naloxone-treated brain sections. Furthermore, morphine-induced analgesia in a hot-plate test showed a leftward shift in the morphine dose-response curve after naloxone treatment. These results suggest that the usefulness of a chronic opioid antagonist dosing regime could be limited by nonspecific effects of the antagonist on ingestive behaviour, an up-regulation of opioid receptors with high antagonist doses, and the resulting supersensitivity to opioid agonists after the discontinuation of the treatment.

[3H]ethylketocyclazocine binding to brain opioid receptor subtypes in alcohol-preferring AA and alcohol-avoiding ANA rats.

We measured brain regional patterns of [3H]ethylketocyclazocine binding to brain opioid receptors in ethanol-naive alcohol-preferring Alko, Alcohol (AA) and alcohol-avoiding Alko, Non-Alcohol (ANA) rats, by using quantitative autoradiography. This agonist ligand labels all opioid receptor subtypes. The proportions of mu- and delta-opioid receptor binding were evaluated by displacing the mu- and delta-opioid receptor components by the peptides Tyr-D-Ala-Gly-N(Me)Phe-Gly-ol (DAMGO, 100 nM) and Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE, 100nM), respectively, the K-component being the naltrexone-sensitive binding left after removal of the above two components. The labeling patterns in the brains of the AA and ANA rats were consistent with the well-known distributions of the opioid receptor subtypes in nonselected rat strains and there was no major difference between the lines. The mu-opioid receptor binding was greater in the AA than ANA rats in several brain regions, most interestingly in the substantia nigra pars reticulata and striatal clusters with elevated shell/core ratios in the nucleus accumbens. The delta-opioid receptor binding did not differ between the lines, whereas the AA rats had more K-opioid receptors than the ANA rats in several brain regions, including limbic areas and basal ganglia. The observed results might indicate altered action of the opioidergic system on dopaminergic pathways in rats with differential alcohol preference.

Brain opioid receptor binding of [3H]CTOP and [3H]naltrindole in alcohol-preferring AA and alcohol-avoiding ANA rats.

We compared mu- and delta-opioid receptor distributions between the brains of alcohol-preferring Alko, Alcohol (AA) and alcohol-avoiding Alko, Non-Alcohol (ANA) rat lines, using autoradiography on brain sections with mu- and delta-opioid receptor antagonist ligands [3H]CTOP and [3H]naltrindole, respectively. The labeling patterns of the ligands were consistent with the known opioid receptor distributions in both rat lines and no major genetic differences were found between the lines. However, the binding density of mu- and delta-opioid receptors differed slightly in several brain areas: in the AA brain sections, limbic areas, such as hippocampus and amygdala, showed decreased mu- and delta-opioid receptor binding, whereas the striatal patches were larger and the substantia nigra showed higher binding density of the mu-receptors compared to the ANA sections. The small differences observed between the rat lines could be due to adaptations to altered endogenous opioid peptide levels or neural circuits, and associated with the differences in alcohol drinking or other behaviors.

Dual modulation of calcium channel current via recombinant alpha2-adrenoceptors in pheochromocytoma (PC-12) cells.

The ability of recombinant rat alpha2D-and alpha2B-adrenoceptors expressed in nerve-growth-factor-differentiated pheochromocytoma PC-12 cells to modulate Ca2+ currents, recorded by the whole-cell patch-clamp technique, has been studied. Ca2+ currents in different cells were either reversibly reduced or increased by dexmedetomidine, an alpha2-adrenergic agonist, in a concentration-dependent manner. Pertussis toxin pretreatment reduced the number of cells that showed an inhibitory response and reduced the magnitude of inhibition. In cells expressing the alpha2B-adrenoceptor, pertussis toxin increased the proportion of cells from which a stimulatory effect on Ca2+ currents could be recorded. The magnitude of the inhibitory responses was unaffected but the stimulatory responses were considerably reduced by the dihydropyridine Ca2+ channel blocker nifedipine (5 microM). All effects of dexmedetomidine were reversible upon wash-out and inhibited by the antagonist rauwolscine. The results support the idea that modulation of voltage-dependent Ca2+ channels in transfected PC-12 cells is mediated by activation of recombinant alpha2D- and alpha2B-adrenoceptors. This receptor activation predominantly causes inhibition of dihydropyridine-insensitive Ca2+ channels via pertussis-toxin-sensitive G proteins. Additionally receptor activation can also lead to stimulation of dihydropyridine-sensitive Ca2+ channels via pertussis-toxin-insensitive mechanisms.

A study of sleep patterns on two Finnish icebreakers, ambulatory recording and automatic analysis.

The effects of noise and vibration on sleep in Finnish ice-breaking ships were studied in healthy volunteer workers and a control group. EEG, EOG and EMG were recorded by means of portable tape recorders. The recordings were analysed by an automatic hybrid system. Both sleep stage parameters and the quantities of single EEG waveforms were used for the evaluation of the sleep quality. Measurements were made before, during and after the ice-breaking season in the winter. Higher amounts of wakefulness and sleep stage 1, and lower amounts of delta and theta activity were found on a night during the ice-breaking season, compared with a night after the season. This was interpreted as indicating a "lightening" of sleep, caused by noise and vibration. No differences between the nights before and during the ice-breaking season were observed. The crew members had an appr. 1 h shorter Time In Bed and Sleep Period Time than the controls also on the nights studied ashore. Because of the small number of subjects the results are not conclusive, even though statistically significant differences were obtained. The delta activity in seconds/minute seems to be a more informative measure than the percentages of the sleep stages S3 and S4. The possibility of using the theta activity as a measure of the length of sleep should be further investigated.