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There are no large scale studies on Epilepsy in populations with Learning disability in Ireland. As many as one fifth of these clients have epilepsy. Aggressive treatment may lead to diminishing returns in terms of symptomatic control, while causing unwanted effects.
1. We aimed to quantify rates of epilepsy, aetiology and anti- epileptic drug (AED) use in our population.
2. To look at degree of disability and correlation with AED use.
3. To look at management/ quality of life issues using a validated instrument.
1. Medline review using search terms Intellectual OR Learning difficult* OR Mental Retard* AND Epilepsy.
2. Simple questionnaire used to identify all clients with Epilepsy. Database analysed using SPSS analysis.
3. 11 cases selected for review looking at qualitative aspects, using Semi structured interview and GEOS scale.
· 210 patients found to have a history of epilepsy (42% of clients).
· Multiple Aetiologies identified. Commonest known Aetiology: Trisomy 21.
· Polypharmacy is common. Most commonly used AED: Sodium Valproate. Mean AED use: 1.595 (SD+- 1.077).
· Clients with Trisomy 21 aged less than 40 tended to be on more medication (2.05, SD= +-1.38) than those over 40 years (1.43, SD= +- 0.89)
· Greater concerns on qualitative measures regarding clients with refractory epilepsy or where epilepsy changed over time.
Our study highlights previously recognised changing patterns in aetiology of Learning Disability and also the changes over time in these clients. More study is required.
Evaluate durability of pregabalin's effect on pain associated with fibromyalgia (FM).
Randomized, double-blind, placebo-controlled trial with 1-week single-blind placebo run-in. Patients meeting ACR diagnostic criteria were randomized to pregabalin 300, 450, or 600 mg/d (BID) or placebo for 14 weeks (2-week dosage escalation; 12-week fixed-dosage). Pain was assessed with a daily pain diary using an 11-point numeric scale. Primary efficacy parameter was the LOCF endpoint mean pain score (MPS). Sensitivity analyses were assessed using the Duration Adjusted Average Change (DAAC) and a Mixed Model Repeated Measurements (MMRM).
745 randomized patients: 95% female, mean age=50 years, median FM duration=10 years, baseline MPS=6.7. Placebo-corrected differences in mean change from baseline to endpoint in MPS: 300mg/d, -0.71 (P=0.0009); 450mg/d, -0.98 (P<0.0001); 600mg/d, -1.00 (P<0.0001). Mean differences from placebo at endpoint (adjusted for treatment duration) over the entire treatment period (DAAC): 300mg/d, -.38, P=0.0200; 450mg/d, -.62; P=0.0001 and 600mg/d,-.57 P<0.0001. In the MMRM analysis, all 3 pregabalin treatment groups demonstrated pain relief by Week 1, and every weekly assessment thereafter, with the exception of 300mg/d treatment group at Week 11. Most common AEs: dizziness (all pregabalin, 35.8% vs placebo, 7.6%); somnolence (18.0% vs 3.8%). Most AEs were mild to moderate and resolved with continued treatment.
Pregabalin demonstrated significant reduction in endpoint MPS in FM patients. The DAAC sensitivity analysis confirmed the robustness of this effect. MMRM analyses demonstrated significant pain relief by Week 1 that was maintained throughout pregabalin treatment.
This study (A0081057) was designed to evaluate the long-term safety and efficacy of pregabalin treatment of fibromyalgia (FM).
In this 1-year, open-label (OL) extension of a 13-week randomized, placebo-controlled trial of pregabalin FM patients had the option of continuing pregabalin at doses of 150 to 600 mg/d. Efficacy was measured by the Short-Form McGill Pain Questionnaire (SF-MPQ), which included sensory and affective pain descriptors, Present Pain Intensity (PPI) index, and a Visual Analog Scale (VAS).
429 of 431 screened patients entered OL treatment, 249 (58%) completed, 70 (16.3%) discontinued due to an adverse event (AE), and 110 (25.7%) discontinued for other reasons. Median duration of treatment with pregabalin was 357 days (range, 1-402 days); 114 received pregabalin for ≥1 year. No clinically meaningful increases in dose were noted over the OL treatment period. Weighted mean dose was 414 mg/d in the first 3 months of treatment and 444 mg/d after 9 months of treatment. SF-MPQ sensory, affective, and total scores were improved relative to baseline, VAS pain score decreased 21 points (0-100 scale), and PPI decreased 0.9 point (0-5 scale). The most frequently reported all-causality AEs were dizziness, somnolence, peripheral edema, and increased weight, most of which were mild to moderate in intensity and of limited duration.
Pregabalin administered for up to 1 year was generally well tolerated by FM patients without evidence of dose increase over time. The sustained improvement in pain measures during OL treatment was consistent with that in shorter term double-blind trials.
Examine the evidence for a relationship between pregabalin effect on pain and baseline anxiety and depressive symptoms in patients with fibromyalgia (FM).
Chronic pain and concomitant anxiety and depressive symptoms are common in patients with FM, as well as in other chronic pain disorders. Pregabalin was effective for treating pain in FM patients in three parallel group RCTs (105, 1056, 1077) where data for anxiety and depressive symptom levels were collected.
Patients meeting ACR criteria for FM with a pain VAS score ≥40 mm were followed for 8-14 weeks in 3 randomized, double-blind, placebo-controlled trials. Patients (N=2022) received 150, 300, 450 or 600mg/d pregabalin or placebo. The primary efficacy parameter was change in endpoint Mean Pain Score (MPS) (range 0 [no pain]-10[worst possible pain]). Regression analyses evaluated whether changes in pain bore any relation to the baseline Hospital Anxiety and Depression Scales (HADS-A) and (HADS-D) levels.
Pregabalin 300, 450, and 600 mg/d, but not 150 mg/d, showed statistically significant improvements in pain compared with placebo (p<0.0001). For each pregabalin treatment group, improvements in pain at endpoint were not found to have a statistically significant association with baseline levels of anxiety or depressive symptoms. Adverse events (AEs) were consistent with known side effects of pregabalin; dizziness and somnolence, mild to moderate in intensity, were the most frequently reported AEs for pregabalin patients.
Pregabalin treatment demonstrated significant improvements in pain regardless of baseline anxiety or depressive symptom levels for patients with FM.
Sleep disturbance is prominent in fibromyalgia (FM). This 14-week, randomized, double-blind, placebo-controlled study, evaluated the effect of pregabalin on pain and sleep-related outcomes in FM.
Patients meeting ACR (FM) diagnostic criteria were randomized to pregabalin 300, 450, or 600mg/d (BID) or placebo for 14 weeks (A0081077). Primary efficacy parameter: LOCF endpoint mean pain score (MPS). At baseline and endpoint, patients completed the Medical Outcomes Sleep (MOS) Sleep Scale. Mean Sleep Quality scores (11-point numeric ratings) were derived from patient daily diaries.
745 randomized patients: 95% female, mean age=50 years, baseline MPS: 6.7. Placebo-corrected differences from baseline to endpoint in MPS were: 300mg/d, -0.71 (p=.0009); 450mg/d, -0.98 (p<.0001); 600mg/d, -1.00 (p<.0001). For MOS Sleep Disturbance, all 3 pregabalin groups demonstrated significant improvements versus placebo (300, 450, and 600 mg/d, -8.91 [p=.0006]; -10.63 [p<.0001]; and -14.93 [p<.0001], respectively). Similar improvements were seen in Sleep Quality (300, 450, and 600mg/d; 0.42, p=0.0030; 0.48, p=.0006; and 0.68, p<.0001 respectively) and MOS Sleep Adequacy (300, 450 and 600mg/d; 5.86, p=.0324; 7.89, p=.0036, and 11.16, p<.0001 respectively). Endpoint Mean Sleep Quality scores across all 3 treatment groups showed significant improvements (300, 450 and 600mg/d; -0.74, p=.0006, -1.12, and -1.35, both p<.0001 respectively). Most common AEs: dizziness (all pregabalin, 35.8% vs placebo, 7.6%); somnolence (18.0% vs 3.8%). Incidence of AEs appeared to be dose-related; most were mild to moderate.
Pregabalin treatment demonstrated significant improvements in pain and patient reported measures of sleep disturbance, adequacy, and quality.
The influence of pharmaceutical industry (PI) on clinical practice and research in psychiatry has been considered a serious problem. Strict rules and guidelines were developed to regulate the interactions between doctors and PI. However, there is an ongoing debate whether these were thoroughly implemented in practice and internalized by physicians. The objective of our study was to assess the attitudes and behaviors of trainees in psychiatry and child & adolescent psychiatry toward PI across Europe. Methodologically, a validated questionnaire with additional items was administered to1444 trainees in 20 European countries. The minimum response rate was set at 60%. We found a high variation across countries in number of interactions between trainees and PI representatives; Portugal and Turkey had the highest number of interactions. The majority (59.76%) agreed that interactions with PI representatives have an impact on physicians’ prescribing behavior; whereas only 29.26% and 19.79% agreed interactions with PI representatives and gifts from PI have impact on their own prescribing behavior, respectively. Most of the gifts were considered appropriate by the majority, except tickets to vacation spot and social dinner at a restaurant. Of the sample, 70.76% think they have not been given sufficient training regarding how to interact with PI representatives. Only less than 20% indicated they have guidelines at institutional or national level. In conclusion, there is substantial interaction between trainees and PI across countries. The majority feel inadequately trained regarding professional interaction with PI, and believes they are immune to the influence of PI.
Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees.
One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire.
The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean) = 0.92, SD = 1.44, range = 0–12) and most in Portugal (M = 19.06, SD = 17.44, range = 0–100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M = 3.30, SD = 1.26 vs. M = 2.39, SD = 1.06 on a 5-point Likert scale: 1 “completely disagree” to 5 “completely agree”). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio) = 1.21, 95%CI = 1.12–1.30 and OR = 1.18, 95%CI = 1.02–1.37).
There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.
Postgraduate medical trainees experience high rates of burnout, but evidence regarding psychiatric trainees is missing. We aim to determine burnout rates among psychiatric trainees, and identify individual, educational and work-related factors associated with severe burnout.
In an online survey psychiatric trainees from 22 countries were asked to complete the Maslach Burnout Inventory (MBI-GS) and provide information on individual, educational and work-related parameters. Linear mixed models were used to predict the MBI-GS scores, and a generalized linear mixed model to predict severe burnout.
This is the largest study on burnout and training conditions among psychiatric trainees to date. Complete data were obtained from 1980 out of 7625 approached trainees (26%; range 17.8–65.6%). Participants were 31.9 (SD 5.3) years old with 2.8 (SD 1.9) years of training. Severe burnout was found in 726 (36.7%) trainees. The risk was higher for trainees who were younger (P < 0.001), without children (P = 0.010), and had not opted for psychiatry as a first career choice (P = 0.043). After adjustment for socio-demographic characteristics, years in training and country differences in burnout, severe burnout remained associated with long working hours (P < 0.001), lack of supervision (P < 0.001), and not having regular time to rest (P = 0.001). Main findings were replicated in a sensitivity analysis with countries with response rate above 50%.
Besides previously described risk factors such as working hours and younger age, this is the first evidence of negative influence of lack of supervision and not opting for psychiatry as a first career choice on trainees’ burnout.
Lieder and Griffiths rightly urge that computational cognitive models be constrained by resource usage, but they should go further. The brain's primary function is to regulate resource usage. As a consequence, resource usage should not simply select among algorithmic models of “aspects of cognition.” Rather, “aspects of cognition” should be understood as existing in the service of resource management.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Utilising routine surveillance data, this study presents a method for generating a baseline comparison that can be used in future foodborne outbreak investigations following a case–case methodology. Salmonella and Campylobacter cases (2012–2015) from Maricopa County, AZ were compared to determine differences in risk factors, symptoms and demographics. For foods and other risk factors, adjusted odds ratios were developed using Campylobacter as the reference. Comparisons were also made for three major Salmonella subtypes, Typhimurium, Enteritidis and Poona as compared with Campylobacter. Salmonella cases were younger, while Campylobacter cases were more Hispanic and female. Campylobacter cases reported consuming peppers, sprouts, poultry, queso fresco, eggs and raw nuts more and reported contact with animal products, birds, visiting a farm or dairy, owning a pet, a sick pet, swimming in a river, lake or pond, or handling multiple raw meats more. Salmonella cases reported visiting a petting zoo and contact with a reptile more. There were significant variations by Salmonella subtype in both foods and exposures. We recommend departments conduct this analysis to generate a baseline comparison and a running average of relevant odds ratios allowing staff to focus on trace-back of contaminated food items earlier in the outbreak investigation process.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls’ AGD. In total, 300 mother–daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.
No existing models of alcohol prevention concurrently adopt universal and selective approaches. This study aims to evaluate the first combined universal and selective approach to alcohol prevention.
A total of 26 Australian schools with 2190 students (mean age: 13.3 years) were randomized to receive: universal prevention (Climate Schools); selective prevention (Preventure); combined prevention (Climate Schools and Preventure; CAP); or health education as usual (control). Primary outcomes were alcohol use, binge drinking and alcohol-related harms at 6, 12 and 24 months.
Climate, Preventure and CAP students demonstrated significantly lower growth in their likelihood to drink and binge drink, relative to controls over 24 months. Preventure students displayed significantly lower growth in their likelihood to experience alcohol harms, relative to controls. While adolescents in both the CAP and Climate groups demonstrated slower growth in drinking compared with adolescents in the control group over the 2-year study period, CAP adolescents demonstrated faster growth in drinking compared with Climate adolescents.
Findings support universal, selective and combined approaches to alcohol prevention. Particularly novel are the findings of no advantage of the combined approach over universal or selective prevention alone.
As we enter the era of gravitational wave astronomy, we are beginning to collect observations which will enable us to explore aspects of astrophysics of massive stellar binaries which were previously beyond reach. In this paper we describe COMPAS (Compact Object Mergers: Population Astrophysics and Statistics), a new platform to allow us to deepen our understanding of isolated binary evolution and the formation of gravitational-wave sources. We describe the computational challenges associated with their exploration, and present preliminary results on overcoming them using Gaussian process regression as a simulation emulation technique.
Hendra virus (HeV) was first described in 1994 in an outbreak of acute and highly lethal disease in horses and humans in Australia. Equine cases continue to be diagnosed periodically, yet the predisposing factors for infection remain unclear. We undertook an analysis of equine submissions tested for HeV by the Queensland government veterinary reference laboratory over a 20-year period to identify and investigate any patterns. We found a marked increase in testing from July 2008, primarily reflecting a broadening of the HeV clinical case definition. Peaks in submissions for testing, and visitations to the Government HeV website, were associated with reported equine incidents. Significantly differing between-year HeV detection rates in north and south Queensland suggest a fundamental difference in risk exposure between the two regions. The statistical association between HeV detection and stockhorse type may suggest that husbandry is a more important risk determinant than breed per se. The detection of HeV in horses with neither neurological nor respiratory signs poses a risk management challenge for attending veterinarians and laboratory staff, reinforcing animal health authority recommendations that appropriate risk management strategies be employed for all sick horses, and by anyone handling sick horses or associated biological samples.
Most empirical studies into the covariance structure of psychopathology have been confined to adults. This work is not developmentally informed as the meaning, age-of-onset, persistence and expression of disorders differ across the lifespan. This study investigates the underlying structure of adolescent psychopathology and associations between the psychopathological dimensions and sex and personality risk profiles for substance misuse and mental health problems.
This study analyzed data from 2175 adolescents aged 13.3 years. Five dimensional models were tested using confirmatory factor analysis and the external validity was examined using a multiple-indicators multiple-causes model.
A modified bifactor model, with three correlated specific factors (internalizing, externalizing, thought disorder) and one general psychopathology factor, provided the best fit to the data. Females reported higher mean levels of internalizing, and males reported higher mean levels of externalizing. No significant sex differences emerged in liability to thought disorder or general psychopathology. Liability to internalizing, externalizing, thought disorder and general psychopathology was characterized by a number of differences in personality profiles.
This study is the first to identify a bifactor model including a specific thought disorder factor. The findings highlight the utility of transdiagnostic treatment approaches and the importance of restructuring psychopathology in an empirically based manner.
Microbial mats are common in polar streams and often dominate benthic biomass. Climate change may be enhancing the variability of stream flows in the Antarctic, but so far studies investigating mat responses to disturbance have been limited in this region. Mat regrowth was evaluated following disturbance by experimentally scouring rocks from an ephemeral McMurdo Dry Valley stream over two summers (2001–02 and 2012–13). Mats were sampled at the beginning and resampled at the end of the flow season. In 2012–13, mats were additionally resampled mid-season along with previously undisturbed controls. In 2001–02 rocks regained 47% of chlorophyll a and 40% of ash-free dry mass by the end of the summer, while in 2012–13 rocks regrew 18% and 27%, respectively. Mat stoichiometry differed between summers, and reflected differences in biomass and discharge. Oscillatoria spp. were greatest on scoured rocks and Phormidium spp. on undisturbed rocks. Small diatoms Humidophila and Fistulifera spp. increased throughout the summer in all mats, with the latter more abundant in scoured communities. Collectively, these data suggest that mats are variable intra-annually, responsive to hydrology and require multiple summers to regrow initial biomass once lost. These results will aid the interpretation of long-term data, as well as inform Antarctic Specially Managed Area protocols.