Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is ...unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics. In subgroups of pre-disposed patients, e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs, the absolute risk of drug-induced arrhythmia may be considerable. On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications were weighted and categorized into three risk categories. Additionally, we suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a prudent follow-up for patients with an increased risk. We believe this clinically manageable guideline might improve safety in the many and rapidly increasing number of patients on psychotropic drugs.
Aim
We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus (T2DM) treated with liraglutide versus comparator diabetes therapies.
Methods
...Twenty‐six‐week data from seven phase 3, randomized trials in the liraglutide T2DM development programme were analysed by trial and treatment group: liraglutide (1.2 and 1.8 mg), active comparator and placebo. Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline; impact of body mass index (BMI) and gastrointestinal (GI) adverse events (AEs) on weight change and correlation of weight change with change in glycosylated haemoglobin (HbA1c).
Results
A number of subjects experienced >5% weight loss during the trials (24.4% liraglutide 1.8 mg and 17.7% liraglutide 1.2 mg; 17.7% exenatide, 10.0% sitagliptin, 3.6−7.0% sulphonylurea, 2.6% thiazolidinedione and 2.6% glargine; 9.9% placebo). More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide. Across trials, higher initial BMI was associated with slightly greater weight loss with liraglutide. Mean weight loss increased slightly the longer GI AEs persisted. Although HbA1c reduction was slightly larger in higher weight loss categories across treatments (including placebo), sample sizes were small and no clear correlation could be determined. Liraglutide‐treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced; thus, not all HbA1c‐lowering effect appears weight mediated.
Conclusions
The majority of liraglutide‐treated T2DM subjects experienced weight loss in this analysis. Weight loss was greater and occurred more in glucagon‐like peptide‐1 receptor agonist‐treated subjects than in active comparator‐treated subjects.
Understanding animal movements is an important factor for the development of meaningful surveillance and control programs, but also for the development of disease spread models. We analysed the ...Danish pig movement network using static and temporal network analysis tools to provide deeper insight in the connection between holdings dealing with pigs, such as breeding and multiplier herds, production herds, slaughterhouses or traders. Pig movements, which occurred between 1st January 2006 and 31st December 2015 in Denmark, were summarized to investigate temporal trends such as the number of active holdings, the number of registered movements and the number of pigs moved. To identify holdings and holding types with potentially higher risk for introduction or spread of diseases via pig movements, we determined loyalty patterns, annual network components and contact chains for the 24 registered holding types. The total number of active holdings as well as the number of pig movements decreased during the study period while the holding sizes increased. Around 60-90% of connections between two pig holdings were present in two consecutive years and around one third of the connections persisted within the considered time period. Weaner herds showed the highest level of in-loyalty, whereas we observed an intermediate level of in-loyalty for all breeding sites and for production herds. Boar stations, production herds and trade herds showed a high level of out-loyalty. Production herds constituted the highest proportion of holdings in the largest strongly connected component. All production sites showed low levels of in-going contact chains and we observed a high level of out-going contact chain for breeding and multiplier herds. Except for livestock auctions, all transit sites also showed low levels of out-going contact chains. Our results reflect the pyramidal structure of the underlying network. Based on the considered disease, the time frame for the calculation of network measurements needs to be adapted. Using these adapted values for loyalty and contact chains might help to identify holdings with high potential of spreading diseases and thus limit the outbreak size or support control or eradication of the considered pathogen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Critical illness is associated with cognitive impairments. Effective treatment or prevention has not been established. The aim of this review was to create a systematic summary of the ...current evidence concerning clinical interventions during intensive care admission to reduce cognitive impairments after discharge.
Methods
Medline, Embase, Cochrane Central, PsycInfo and Cinahl were searched. Inclusion criteria were studies assessing the effect of interventions during intensive care admission on cognitive function in adult patients. Studies were excluded if they were reviews or reported solely on survivors of cardiac arrest, stroke or traumatic brain injury.
Results
Of 4877 records were identified. Seven studies fulfilled the eligibility criteria. The interventions described covered strategies for enteral nutrition, fluids, sedation, weaning, mobilization, cognitive activities, statins and sleep quality improvement. Data were synthesized to provide an overview of interventions, quality, follow‐up assessments and neuropsychological outcomes.
Conclusion
None of the interventions had significant positive effects on cognitive impairments following critical illness. Quality was negatively affected by study limitations, imprecision and indirectness in evidence. Clinical research on cognition is feasible, but large, well designed trials with a specific aim at reducing cognitive impairments are needed.
Background
Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors’ preferences for supplementing oxygen are inadequately described. The aim was to identify ICU ...doctors’ preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients.
Methods
In April to August 2016, an online multiple‐choice 17‐part‐questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e‐mails were sent. The study ended in October 2016.
Results
The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2); and 23% preferred SaO2. Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets.
Conclusion
Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.
Background Mutations in the postsynaptic transmembrane protein neuroligin-3 are highly correlative with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Fear learning is well ...studied in models of these disorders, however differences in fear response behaviours are often overlooked. We aim to examine fear behaviour and its cellular underpinnings in a rat model of ASD/ID lacking Nlgn3. Methods This study uses a range of behavioural tests to understand differences in fear response behaviour in Nlgn3.sup.-/y rats. Following this, we examined the physiological underpinnings of this in neurons of the periaqueductal grey (PAG), a midbrain area involved in flight-or-freeze responses. We used whole-cell patch-clamp recordings from ex vivo PAG slices, in addition to in vivo local-field potential recordings and electrical stimulation of the PAG in wildtype and Nlgn3.sup.-/y rats. We analysed behavioural data with two- and three-way ANOVAS and electrophysiological data with generalised linear mixed modelling (GLMM). Results We observed that, unlike the wildtype, Nlgn3.sup.-/y rats are more likely to response with flight rather than freezing in threatening situations. Electrophysiological findings were in agreement with these behavioural outcomes. We found in ex vivo slices from Nlgn3.sup.-/y rats that neurons in dorsal PAG (dPAG) showed intrinsic hyperexcitability compared to wildtype. Similarly, stimulating dPAG in vivo revealed that lower magnitudes sufficed to evoke flight behaviour in Nlgn3.sup.-/y than wildtype rats, indicating the functional impact of the increased cellular excitability. Limitations Our findings do not examine what specific cell type in the PAG is likely responsible for these phenotypes. Furthermore, we have focussed on phenotypes in young adult animals, whilst the human condition associated with NLGN3 mutations appears during the first few years of life. Conclusions We describe altered fear responses in Nlgn3.sup.-/y rats and provide evidence that this is the result of a circuit bias that predisposes flight over freeze responses. Additionally, we demonstrate the first link between PAG dysfunction and ASD/ID. This study provides new insight into potential pathophysiologies leading to anxiety disorders and changes to fear responses in individuals with ASD. Keywords: Fear, Freezing, Flight, Autism, Intellectual disability, Periaqueductal grey, Neuroligin-3
Patients’ opinions on outcomes following critical illness Nedergaard, H. K.; Haberlandt, T.; Reichmann, P. D. ...
Acta anaesthesiologica Scandinavica,
April 2018, 2018-Apr, 2018-04-00, 20180401, Letnik:
62, Številka:
4
Journal Article
Recenzirano
Background
Our aim was to explore which outcomes are most important to patients following ICU‐discharge, and to explore whether intensive care unit (ICU)‐nurses and anesthesiologists are aware of ...patients’ priorities.
Methods
First, interviews with adult ICU‐survivors were conducted until data saturation was achieved (10 interviews), and six areas with 36 items were identified. Second, interviews with another eight ICU‐survivors were conducted, narrowing the list to 20. Finally, patients (inclusion criteria: consecutive adults, medical and surgical, ICU‐admission > 5 days, 2–8 months post‐ICU discharge) rated the items, as did ICU‐nurses and anesthesiologists.
Results
A total of 32 patients participated (44% women, medians: age 70.5, time since discharge 179 days, length of stay in ICU 9 days, APACHEII 19.5). The three most important outcomes defined by patients were: lack of physical strength, fatigue, and decreased walking distance. The top three for ICU‐nurses (54 participants) were: fatigue, difficulties concentrating, sadness/depression, and for anesthesiologists (17 participants): fatigue, difficulties in activities of daily living, and lack of physical strength.
Conclusion
Patients chose lack of physical strength, fatigue, and decreased walking distance as the three most important outcomes following critical illness. Physicians had a higher focus on these physical impairments than ICU‐nurses.
The Earth's mantle is isotopically heterogeneous on length scales ranging from centimetres to more than 104 kilometres. This heterogeneity originates from partial melt extraction and plate tectonic ...recycling, whereas stirring during mantle convection tends to reduce it. Here we show that mid-ocean ridge basalts from 2,000 km along the southeast Indian ridge (SEIR) display a bimodal hafnium isotopic distribution. This bimodality reveals the presence of ancient compositional striations (streaks) in the Indian Ocean upper mantle. The number density of the streaks is described by a Poisson distribution, with an average thickness of ∼40 km. Such a distribution is anticipated for a well-stirred upper mantle, in which heterogeneity is continually introduced by plate tectonic recycling, and redistributed by viscous stretching and convective refolding.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Genome‐wide association studies have identified genetic variants associating with BMI, however, it is un‐clarified whether the same variants also influence body weight fluctuations.
Methods
...Among 3,982 adult individuals that attended both a baseline and a five‐year follow‐up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS.
Results
The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33‐0.58) kg (P = 2.7 × 10−12), corresponding to a body weight difference of 3.41 (2.21‐4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed.
Conclusion
The GRS associated with body weight cross‐sectionally, but not with changes over a five‐year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.