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Introduction: Acute migraine headaches are common causes of presentation to the emergency department (ED). There is great variability in the efficacy of the available parenteral agents to manage pain, though triptans are among the recommended treatments. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review examined pain management in emergency settings and assessed the effectiveness of triptan agents. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Pain scale scores were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using a random effects model; heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Pain was measured within the ED or equivalent acute care setting using a variety of pain scales, most commonly the 0-10 cm or 100 mm visual analog scale. Four studies compared pain scores between patients receiving sumatriptan vs. other agents, of which, patients receiving sumatriptan reported higher pain scale scores (SMD = 0.53; 95% CI: 0.04, 1.02; I2 = 80%). In particular, patients receiving sumatriptan reported higher pain scale scores than patients receiving metoclopramide (SMD = 0.68; 95% CI: 0.31, 1.04; n = 1) or ketorolac (SMD = 1.39; 95% CI: 0.56, 2.21; n = 1). Overall, studies comparing anti-inflammatory agents (i.e., ketorolac or dexketoprofen) to other agents reported improved pain scale scores among patients receiving anti-inflammatory agents (SMD = -0.38; 95% CI: -0.73, -0.03; I2 = 66%; n = 5). Conclusion: Limited evidence suggests that patients treated with metoclopramide or anti-inflammatory agents experience greater pain reduction compared to patients treated with sumatriptan. This review will conduct a network analysis of parenteral agents to examine the comparative effectiveness of parenteral agents to manage pain among patients with acute migraine. Further analysis will also consider the balance between efficacy and adverse events.
Introduction: Although a variety of parenteral agents exist for the treatment of acute migraine, relapse after an emergency department (ED) visit is still a common occurrence. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review focused on those studies aiming a reduction in relapse after an ED visit. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to identify comparative studies to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Relapse was reported in 44 (38%) included studies and occurred commonly in patients receiving placebo or no interventions (median = 39%; IQR: 14%, 47%). Overall, no differences in headache relapse were found between patients receiving sumatriptan or placebo (RR = 1.09; 95% CI: 0.55, 2.17; I2 = 93%; n = 8). Conversely, patients receiving neuroleptic agents experienced fewer relapses compared to placebo (RR = 0.27; 95% CI: 0.12, 0.58; I2 = 0%; n = 3); however, patients receiving neuroleptics reported an increase in adverse events (RR = 1.87; 95% CI: 1.17, 3.00; I2 = 0%; n = 3). Compared to placebo, patients receiving dexamethasone were less likely to experience a headache recurrence (RR = 0.71; 95% CI: 0.53, 0.95; I2 = 60%, n = 9); however, no differences were found in reported adverse events (RR = 1.09; 95% CI: 0.81, 1.47; I2 = 0%; n = 3). Conclusion: Relapse is a common occurrence for patients with migraine headaches. This review found patients receiving neuroleptics or dexamethasone experienced fewer headache recurrences. Conversely, triptan agents appear to have minimal effect on reducing the risk for headache recurrence following discharge from an acute care setting. Limited available data on adverse events is an important limitation to inform decision-making. Guidelines should be revised to reflect these results.
Watching videotaped personal compulsions together with a therapist might enhance the effect of cognitive–behavioural therapy in obsessive–compulsive disorder (OCD) but little is known about how patients experience this.
To performed a qualitative study that describes how watching these videos influences motivation for treatment and whether patients report any adverse events.
In this qualitative study, data were gathered in semi-structured interviews with 24 patients with OCD. The transcripts were coded by two researchers. They used a combination of open and thematic coding and discrepancies in coding were discussed.
The experience of watching videos with personal compulsions helped patients to realise that these compulsions are aberrant and irrational. Patients report increased motivation to resist their OCD and to adhere to therapy. No adverse events were reported.
Videos with personal compulsions create more awareness in patients with OCD that compulsions are irrational, leading to enhanced motivation for treatment.
Radiocarbon (14C or carbon-14, half-life 5730 yr) is a key radionuclide in the assessment of the safety of a geological disposal facility (GDF) for radioactive waste. In particular, the radiological impact of gaseous carbon-14 bearing species has been recognized as a potential issue. Irradiated steels are one of the main sources of carbon-14 in the United Kingdom’s radioactive waste inventory. However, there is considerable uncertainty about the chemical form(s) in which the carbon-14 will be released. The objective of the work was to measure the rate and speciation of carbon-14 release from irradiated 316L(N) stainless steel on leaching under high-pH anoxic conditions, representative of a cement-based near field for low-heat generating wastes. Periodic measurements of carbon-14 releases to both the gas phase and to solution were made in duplicate experiments over a period of up to 417 days. An initial fast release of carbon-14 from the surface of the steel is observed during the first week of leaching, followed by a drop in the rate of release at longer times. Carbon-14 is released primarily to the solution phase with differing fractions released to the gas phase in the two experiments: about 1% of the total release in one and 6% in the other. The predominant dissolved carbon-14 releases are in inorganic form (as 14C-carbonate) but also include organic species. The predominant gas-phase species are hydrocarbons with a smaller fraction of 14CO (which may include some volatile oxygen-containing carbon-species). The experiments are continuing, with final sampling and termination planned after leaching for a total of two years.
The assessment of the seismic hazard and risk associated with the extraction of gas from the Groningen field involves a chain of modelling efforts. The first step is a description of the 3D distribution of reservoir properties in the reservoir – the static reservoir model – and is the subject of this paper. Consecutive steps in the chain of models are described elsewhere in this volume. The construction of a static reservoir model is not strictly a scientific endeavour, but many of the applied modelling techniques are underpinned by extensive scientific research. This paper aims to give a general introduction to the approach followed by NAM to build static models for the Groningen field. More detailed accounts of the applied modelling techniques, the assessment of associated uncertainties or the usage of multiple modelling scenarios are beyond the scope of the current paper, but are referenced in the text.
In fully developed evaporite cycles, effective viscosity contrasts of up to five orders of magnitude are possible between different layers, but the structures and mechanics in evaporites with such extreme mechanical stratification are not well understood. The Zechstein 3 unit in the Veendam salt pillow in the Netherlands contains anhydrite, halite, carnallite and bischofite, showing this extreme mechanical stratification. The Veendam Pillow has a complex multiphase salt tectonic history as shown by seismic reflection data: salt withdrawal followed by convergent flow into the salt pillow produced ruptures and folds in the underlying Z3-anhydrite–carbonate stringer and deformed the soft Z3-1b layer
We analysed a unique carnallite- and bischofite-rich drill core from the soft Z3-1b layer by macroscale photography, bulk chemical methods, X-ray diffraction and optical microscopy. Results show high strain in the weaker bischofite- and carnallite-rich layers, with associated dynamic recrystallisation at very low differential stress, completely overprinting the original texture. Stronger layers formed by alternating beds of halite and carnallite show complex recumbent folding on different scales commonly interrupted by sub-horizontal shear zones with brittle deformation, veins and boudinage. We attribute this tectonic fragmentation to be associated with a softening of the complete Z3-1b subunit during its deformation. The result is a tectonic mélange with cm- to 10 m-size blocks with frequent folds and boudinage. We infer that these structures and processes are common in deformed, rheologically strongly stratified evaporites.
The course of illness in obsessive–compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD.
The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support.
Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22–3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01–2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09–0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08–1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03–1.16, p = 0.003) increased the risk of remaining chronic.
External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.
The most popular beef breed in South Africa is the Bonsmara, a locally developed composite breed adapted to sub-tropical conditions. The establishment of a genomic reference population is currently ongoing for the application of genomic selection. To date, 583 Bonsmara cattle (388 bulls and 195 cows) have been genotyped with the GeneSeek® Genomic Profiler Bovine HD™ Chip (GGP-HD) 80 K chip, and the population structure of the reference population was studied. The average minor allele frequency for the Bonsmara was 0.280 across 56 248 autosomal single-nucleotide polymorphisms (SNPs), whereas the observed and expected heterozygosity values were 0.361 and 0.365, respectively. After pruning the data set for SNPs in linkage disequilibrium, 19 119 SNPs were retained, averaging 659 SNPs per autosomal chromosome. This generated an average SNP density of 1 SNP per 90 kb. Structure analysis revealed a non-homogenous population with a high level of genetic admixture, which may negatively influence genomic breeding value prediction accuracy. Genotyping of a further 990 Bonsmara cattle are pending, using the GeneSeek® GGP-HD 150 K chip. As more animals will be added to the reference population, the profile of the reference population are expected to change in such a way to ensure improved genomic estimated breeding value accuracies.
The major histocompatibility complex region has been implicated in explaining some of the variation observed in adaptability and tick susceptibility of cattle. The bovine leukocyte antigen region of 192 cattle representing indigenous, composite and exotic breeds used in commercial beef production in Namibia and South Africa was investigated using four microsatellite markers. Ticks counted under the tail were taken as an indicator of tick susceptibility. Tick scores of all but one population was low (11 to 20 ticks), with only the South African Bonsmara population having an average score of 31 to 40 ticks per animal. The observed variation based on four microsatellite markers ranged from 5.5 alleles in Namibian Afrikaner to 7.7 alleles in South African Nguni and Bonsmara cattle. Unbiased heterozygosity values ranged from 0.66 (Namibian Afrikaner) to 0.76 (South African Bonsmara). Structure analyses grouped the five populations into three indistinct clusters with limited genetic variation between the populations.
Background: The number of refugees is the highest ever worldwide. Many have experienced trauma in home countries or on their escape which has mental health sequelae. Intrusive memories comprise distressing scenes of trauma which spring to mind unbidden. Development of novel scalable psychological interventions is needed urgently. Aims: We propose that brief cognitive science-driven interventions should be developed which pinpoint a focal symptom alongside a means to monitor it using behavioural techniques. The aim of the current study was to assess the feasibility and acceptability of the methodology required to develop such an intervention. Method: In this study we recruited 22 refugees (16–25 years), predominantly from Syria and residing in Sweden. Participants were asked to monitor the frequency of intrusive memories of trauma using a daily diary; rate intrusions and concentration; and complete a 1-session behavioural intervention involving Tetris game-play via smartphone. Results: Frequency of intrusive memories was high, and associated with high levels of distress and impaired concentration. Levels of engagement with study procedures were highly promising. Conclusions: The current work opens the way for developing novel cognitive behavioural approaches for traumatized refugees that are mechanistically derived, freely available and internationally scalable.
Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.
In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.
We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.
TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.
Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.
A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.
A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.
Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.
We aimed to identify barriers for meeting the fruit, vegetable and fish guidelines in older Dutch adults and to investigate socio-economic status (SES) differences in these barriers. Furthermore, we examined the mediating role of these barriers in the association between SES and adherence to these guidelines.
Longitudinal Aging Study Amsterdam (LASA), the Netherlands.
We used data from 1057 community-dwelling adults, aged 55–85 years. SES was measured by level of education and household income. An FFQ was used to assess dietary intake and barriers were measured with a self-reported lifestyle questionnaire.
Overall, 48·9 % of the respondents perceived a barrier to adhere to the fruit guideline, 40·0 % for the vegetable and 51·1 % for the fish guideline. The most frequently perceived barriers to meet the guidelines were the high price of fruit and fish and a poor appetite for vegetables. Lower-SES groups met the guidelines less often and perceived more barriers. The association between income and adherence to the fruit guideline was mediated by ‘perceiving any barrier to meet the fruit guideline’ and the barrier ‘dislike fruit’. The association between income and adherence to the fish guideline was mediated by ‘perceiving any barrier to meet the fish guideline’ and the barrier ‘fish is expensive’.
Perceived barriers for meeting the dietary guidelines are common in older adults, especially in lower-SES groups. These barriers and in particular disliking and cost concerns explained the lower adherence to the guidelines for fruit and fish in lower-income groups in older adults.
Anxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI.
Subjects with MCI (n=268) were selected from the ‘Development of screening guidelines and criteria for pre-dementia Alzheimer's disease’ (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42) protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.
Depressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.3] and t-tau (OR 2.6, 95% CI 1.9–3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0–4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1–2.3; irritability: OR 2.2, 95% CI 1.5–3.3). Symptoms of depression and apathy were not related to any of the CSF markers.
In subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.
Loneliness has a significant influence on both physical and mental health. Few studies have investigated the possible associations of loneliness with mortality risk, impact on men and women and whether this impact concerns the situation of being alone (social isolation), experiencing loneliness (feeling lonely) or both. The current study investigated whether social isolation and feelings of loneliness in older men and women were associated with increased mortality risk, controlling for depression and other potentially confounding factors.
In our prospective cohort study of 4004 older persons aged 65–84 years with a 10-year follow-up of mortality data a Cox proportional hazard regression analysis was used to test whether social isolation factors and feelings of loneliness predicted an increased risk of mortality, controlling for psychiatric disorders and medical conditions, cognitive functioning, functional status and sociodemographic factors.
At 10 years follow-up, significantly more men than women with feelings of loneliness at baseline had died. After adjustment for explanatory variables including social isolation, the mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence interval (CI) 1.04–1.63] in men and 1.04 (95% CI 0.90–1.24) in women. No higher risk of mortality was found for social isolation.
Feelings of loneliness rather than social isolation factors were found to be a major risk factor for increasing mortality in older men. Developing a better understanding of the nature of this association may help us to improve quality of life and longevity, especially in older men.
SiGe island layers have been created by post growth anneal on supercritical layers grown at low temperatures (500°C) and high hydrogen pressures (40 Torr). The epitaxial growth has been performed in a commercially available single wafer RPCVD reactor using SiH2Cl2 and GeH4 as precursor gasses. SiGe layers grown under these conditions exceed the critical thickness for the onset of elastic relaxation reported for lower hydrogen pressures as well as the critical thickness for plastic relaxation by more than one order of magnitude. A subsequent anneal step is used to form the islands. This procedure allows some degree of control in the formation of SiGe islands. High island densities and uniform size distributions were achieved. Photoluminescence as well as electroluminescence measurements of these layers show strong emission from SiGe.
The boron out-diffusion into the Si collector of SiGe HBT's with implanted emitters is compensated by an epitaxially grown n+ phosphorus peak effectively positioned adjacent to the as-grown boron peak. Detrimental barrier formation is suppressed in devices with base sheet resistance 3.3 k.Ω and cut-off frequency of 31 GHz.