The lockdown experience scale for students (LESS).

BACKGROUND: The Covid-19 pandemic has resulted in many student populations learning online in lockdown. While the mental health consequences of lockdown are increasingly understood, the core features of 'cabin fever' - the experience of lockdown - are poorly described. METHODS: We conducted a questionnaire survey of 649 undergraduate medicine and health sciences students. Item content was developed based on current literature and input from student representatives. RESULTS: Mokken scaling identified seven questions that together formed a strongly unidimensional scale which comprised two domains: social isolation/cabin fever and demotivation / demoralisation. Scale scores were significantly associated with depression, self-rated mental health, impaired study efficacy and doomscrolling. CONCLUSIONS: The adverse effects of lockdown on student wellbeing appear to be driven to an important extent by an experience of isolation and demotivation that corresponds to narrative descriptions of cabin fever. In the foreseeable event of future pandemics, these experiences are a promising target for health promotion in students studying in lockdown.

Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy.

Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection of an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models of epilepsy. In this study, we used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma. Intraperitoneal and intravenous injection of Ant-134 reached the hippocampus and blocked seizure-induced upregulation of miR-134. A single intraperitoneal injection of Ant-134 at 2 h after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at 3 months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. In vivo knockdown of LIM kinase-1 (Limk-1) increased seizure frequency in Ant-134-treated mice, implicating de-repression of Limk-1 in the antagomir mechanism. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces long-lasting seizure-suppressive effects after systemic injection in mice when timed with BBB disruption and may be a clinically viable approach for this and other disease-modifying microRNA therapies.

Childhood trauma and adult mental disorder: A systematic review and meta-analysis of longitudinal cohort studies.

OBJECTIVE: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood. METHODS: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained. RESULTS: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed. CONCLUSION: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.

Antagonizing Increased miR-135a Levels at the Chronic Stage of Experimental TLE Reduces Spontaneous Recurrent Seizures.

Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The antiepileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. miRNAs, a class of small noncoding RNAs which control gene expression at the post-transcriptional level, play a key role in the pathogenesis of mTLE and other epilepsies. Although manipulation of miRNAs at acute stages has been reported to reduce subsequent spontaneous seizures, it is uncertain whether targeting miRNAs at chronic stages of mTLE can also reduce seizures. Furthermore, the functional role and downstream targets of most epilepsy-associated miRNAs remain poorly understood. Here, we show that miR-135a is selectively upregulated within neurons in epileptic brain and report that targeting miR-135a in vivo using antagomirs after onset of spontaneous recurrent seizures can reduce seizure activity at the chronic stage of experimental mTLE in male mice. Further, by using an unbiased approach combining immunoprecipitation and RNA sequencing, we identify several novel neuronal targets of miR-135a, including Mef2a Mef2 proteins are key regulators of excitatory synapse density. Mef2a and miR-135a show reciprocal expression regulation in human (of both sexes) and experimental TLE, and miR-135a regulates dendritic spine number and type through Mef2. Together, our data show that miR-135a is target for reducing seizure activity in chronic epilepsy, and that deregulation of miR-135a in epilepsy may alter Mef2a expression and thereby affect synaptic function and plasticity.SIGNIFICANCE STATEMENT miRNAs are post-transcriptional regulators of gene expression with roles in the pathogenesis of epilepsy. However, the precise mechanism of action and therapeutic potential of most epilepsy-associated miRNAs remain poorly understood. Our study reveals dramatic upregulation of the key neuronal miRNA miR-135a in both experimental and human mesial temporal lobe epilepsy. Silencing miR-135a in experimental temporal lobe epilepsy reduces seizure activity at the spontaneous recurrent seizure stage. These data support the exciting possibility that miRNAs can be targeted to combat seizures after spontaneous seizure activity has been established. Further, by using unbiased approaches novel neuronal targets of miR-135a, including members of the Mef2 protein family, are identified that begin to explain how deregulation of miR-135a may contribute to epilepsy.

Intestinal parasitosis, anaemia and risk factors among pre-school children in Tigray region, northern Ethiopia.

BACKGROUND: Intestinal parasitic infections (IPIs) and anaemia are major health problems. This study assessed the prevalence of intestinal parasitic infections, anaemia and associated factors among pre-school children in rural areas of the Tigray region, northern Ethiopia. METHODS: A community based cross-sectional study was conducted among 610 pre-school children in rural communities of Northern Ethiopia from June 2017 to August 2017. Stool specimens were examined for the presence of trophozoites, cysts, oocysts, and ova using direct, formal-ethyl acetate concentration, Kato-Katz, and Ziehl-Neelsen techniques. Haemoglobin was measured using a HemoCue spectrometer. RESULTS: Among the 610 participating pre-school children in the study, the prevalence of IPIs and anaemia were 58% (95% conference interval (CI): 54.1-61.9%) and 21.6% (95% CI: 18.5-25.1%), respectively. Single, double, and triple parasitic infections were seen in 249 (41, 95% CI: 37-45%), 83 (14, 95% CI: 11-17%), and 22 (3.6, 95% CI: 2.4-5.4%) children, respectively. Of the seven intestinal parasitic organisms recorded from the participants, Entamoeba histolytica/dispar was the most prevalent 220 (36.1%) followed by Giardia lamblia 128 (20.1%), and Hymenolepis nana 102 (16.7%). Mixed infections were common among G. lamblia, E. histolytica/dispar and Cryptosporidium spp. oocyst. Intestinal parasitic infection prevalence increased from 47% in children aged 6-11 months to 66% in those aged 48-59 months; the prevalence ratio (PR) associated with a one-year increase in age was 1.08 (95% CI: 1.02-1.14, p = 0.009). Age-adjusted prevalence was higher in children who had been dewormed (PR = 1.2; 95% CI: 1.00-1.4, p = 0.045), and lower in households having two or more children aged under five (PR = 0.76, 95% CI: 0.61-0.95, p = 0.015). Anaemia rose from 28% in children aged 6-11 months to 43% in those aged 12-23 months, then fell continuously with age, reaching 7% in those aged 48-59 months. Age adjusted, anaemia was more prevalent in households using proper disposal of solid waste (PR = 1.5, 95% CI: 0.1-2.10, p = 0.009) while eating raw meat (PR = 0.49, 95% CI: 0.45-0.54, p = 0.000), any maternal education (PR = 0.64 95% CI: 0.52-0.79, p = 0.000), and household water treatment (PR = 0.75, 95% CI: 0.56-1.0, p = 0.044) were associated with lower prevalence of anaemia. CONCLUSIONS: More than half of the children were infected with intestinal parasites, while anaemia prevalence was concentrated in the 12-23 month age group. This study has identified a number of potentially modifiable risk factors to address the significant prevalence of IPIs and anaemia in these children. Improvements in sanitation, clean water, hand hygiene, maternal education could address both short and long-term consequences of these conditions in this vulnerable population.

Congenital muscular torticollis: the reliability of visual estimation in the assessment of cervical spine active rotation and head tilt by physiotherapists and the impact of clinical experience.

There is a lack of reliable and valid measurement tools to assess neck function in infants with congenital muscular torticollis, and most physiotherapists use visual estimation, which has not been adequately tested for reliability in this population. We examined the reliability of visual estimation of head tilt and active neck rotation in the upright position, on infants with congenital muscular torticollis by physiotherapists. We recruited 31 infants and 26 physiotherapists. Therapists rated videos of infants' head position in the frontal plane (tilt) and transverse plane (active rotation) using visual estimation, on two occasions at least one week apart. Overall, inter-rater reliability was good (mean ICC, 0.68 ± 0.20; mean SEM, 5.1° ± 2.1°). Rotation videos had better reliability (mean ICC, 0.79 ± 0.14) than head tilt videos (mean ICC, 0.58 ± 0.20). Intra-rater reliability was excellent (mean ICC, 0.85 ± 0.08). Both head tilt and rotation had excellent reliability (mean ICC, 0.84 ± 0.08 for head tilt and 0.85 ± 0.09 for rotation). There was no correlation between intra-rater reliability and clinical experience.Conclusion Visual estimation had excellent intra-rater reliability in the assessment of neck active rotation and head tilt on infants with congenital muscular torticollis. Visual estimation had acceptable inter-rater reliability in the assessment of neck active rotation but not of head tilt. There was a wide variation in reliability with no correlation between reliability and clinical experience. Assessment tools for head tilt that are more psychometrically robust should be developed. What is Known: • A thorough assessment of infants presenting with torticollis is essential, using assessment tools with robust psychometric properties • Visual estimation is the most commonly used method of assessment of neck function in infants with torticollis What is New: • Visual estimation had excellent intra-rater reliability in the assessment of neck active rotation and head tilt in the upright position in videos of infants and acceptable inter-rater reliability in the assessment of rotation but not of head tilt • Physiotherapists' clinical experience had minimal relationship with reliability.

Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients.

Aspirin non-response is associated with poor outcome but there is no agreement between the different methods to asses it. Weight has been shown to be a predictor of poor response but only using one method. In this study, we determine the effects of weight on different assays of platelet function. The response to aspirin was determined in 138 cardiology patients using serum thromboxane, arachidonic acid-induced platelet aggregation and VerifyNow©. Twenty-five percent of patients showed an inadequate response to aspirin in at least one assay on the initial test. After ensuring patient compliance only 5% of patients were considered to be non-responders. Only 9% of non-responders were non-responsive in all three assays. When switched to plain aspirin, only 2% of patients were non-responsive. All patients responded adequately to 150 mg aspirin. The non-responders were significantly heavier than responders (78.5 kg ± 14.0 (SD); BMI: 28.4 kg/m2± 4.4 v's 102.6 kg ± 20.6, P = .0016; BMI: 38.3 kg/m2 ± 7.6, P= .0015). A rule-based approach of using plain aspirin in patients over 90 kg or BMI 32 along with patient education to ensure compliance will ensure that all patients respond to their aspirin without the need for testing.

Factors influencing specialty choice and the effect of recall bias on findings from Irish medical graduates: a cross-sectional, longitudinal study.

BACKGROUND: Despite being a vital part of medical workforce planning and development, how medical students and graduates choose their career specialty is still not well understood. This study aimed to identify the factors medical graduates consider important influences in their choice of specialty after their first year of practice, and to test the validity of relying on respondent recall to measure changes in specialty choice. METHODS: The baseline survey was administered online to all final year students in Ireland's six medical schools. Those who consented to follow-up (n = 483) were surveyed 18 months later (June 2018), during the final month of first year of practice. RESULTS: The baseline survey had a 67% (n = 483) response rate. At the follow-up survey, (n = 232, 48% response rate) the top specialty choices were: Medicine, n = 54 (26%); Surgery, n = 34 (16%); General Practice, n = 28 (13%); Anaesthesia, n = 16 (8%) and Paediatrics, n = 14 (7%). Of the 49 respondents (28%) reporting a change of specialty since baseline, 13 (27%) selected the same specialty in both surveys; of the 121 (69%) reporting no change, 22 (18%) selected a different specialty at follow-up. Over 90% of respondents rated as 'important or 'very important': 'Own aptitude', 'Work-life balance' and 'What I really want to do'. Over 75% rated as 'not at all', or 'not very important' 'Current financial debt' and 'Inclinations before medical school'. When adjusted for sex and age, compared with Medicine, General Practice rated as more important: continuity of patient care (RRR 3.20 CI(1.59-6.41), p = 0.001); working hours/conditions (RRR 4.61 CI(1.03-20.60), p = 0.045) and a career that fit their domestic circumstances (RRR 3.19 CI(1.27-8.02), p = 0.014). Those choosing Surgery rated as less important: patient contact (RRR 0.56 CI(0.33-0.95), p = 0.033) and working hours/conditions (RRR 0.55 CI(0.31-0.96), p = 0.035). CONCLUSIONS: The different demographic and motivational profiles by specialty choice are consistent with other studies suggesting a distinct profile for doctors intending to enter General Practice. In addition, our results suggest longitudinal study designs guard against recall bias and so provide more robust medical workforce models to inform and direct recruitment drives and interventions in future medical workforce planning.

The impacts of training pathways and experiences during intern year on doctor emigration from Ireland.

BACKGROUND: Emigration of domestically-trained health professionals is widespread, including in Ireland which has the highest rate of medical graduates in the OECD. Ireland's failure to retain graduates necessitates high levels of international recruitment. This study aimed to identify factors associated with recently graduated doctors' intention to migrate, focusing on their work experiences during the mandatory post-graduation year, their wellbeing, and their perceptions of postgraduate training in Ireland. METHODS: A baseline survey was administered online to all final year students in Ireland's six medical schools. A subsequent sweep surveyed those who consented to follow-up (n = 483) during the final month of first year of practice. RESULTS: Of the 232 respondents (48% response rate), 210 (94%) were Irish passport holders. Of these, only 36% intended to remain in Ireland after their internship, 57% intended to leave but return later, and 7% intended to leave permanently. A strong predictor of intention was study pathway: 60% of Graduate Entry Medicine (GEM) graduates and 25% of Direct Entry Medicine (DEM) graduates intended to remain in Ireland. Equal proportions intended to leave permanently (8% DEM, 6% GEM). Being a GEM graduate significantly reduced the likelihood of leaving to return (relative risk ratio (RRR) 0.20, 95% confidence interval (CI) (0.11-0.39), p < 0.001). When adjusted for study pathway, a negative experience as an intern increased the likelihood of leaving to return (RRR 1.16 CI (1.00-1.34), p = 0.043) and leaving permanently (1.54 (1.15-2.04), p = 0.003). Similarly, experience of callousness was associated with leaving to return (1.23 (1.03-1.46), p = 0.023) and leaving permanently (1.77 (1.24-2.53), p = 0.002), as was burnout with leaving permanently (1.57 (1.08-2.27), p = 0.017). Those planning to specialise in Medicine versus General Practice were more likely to leave and return (3.01 (1.09-8.34), p = 0.034). Those with negative perceptions of training in Ireland were more likely to leave and return (1.16 (1.01-1.34), p = 0.037); a positive perception reduced the likelihood of leaving permanently (0.50 (0.26-0.94), p = 0.032). CONCLUSIONS: Increasing GEM training places might improve Ireland's retention of domestically-trained doctors, reducing reliance on non-EU-trained doctors. However, improvements in the working experiences, perceptions of training, and protection of wellbeing are essential for retaining this highly sought-after and geographically mobile cohort.

Peer assessment to improve medical student's contributions to team-based projects: randomised controlled trial and qualitative follow-up.

BACKGROUND: Medical schools increasingly incorporate teamwork in their curricula but medical students often have a negative perception of team projects, in particular when there is unequal participation. The purpose of this study is to evaluate whether a novel peer evaluation system improves teamwork contributions and reduces the risk of students "free loading". METHODS: A cluster randomised controlled trial (RCT) with qualitative follow up enrolled 37 teams (n = 223 students). Participating teams were randomised to intervention group (19 teams) or control group (18 teams). The validated Comprehensive Assessment Team Member Effectiveness (CATME) tool was used as the outcome measure, and was completed at baseline (week 2) and at the end of the project (week 10). The team contribution subscale was the primary outcome, with other subscales as secondary outcomes. Six focus group discussions were held with students to capture the team's experiences and perceptions of peer assessment and its effects on team work. RESULTS: The results of the RCT showed that there was no difference in team contribution, and other forms of team effectiveness, between intervention and control teams. The focus group discussions highlighted students' negative attitudes, and lack of implementation of this transparent, points-based peer assessment system, out of fear of future consequences for relationships with peers. The need to assess peers in a transparent way to stimulate open discussion was perceived as threatening by participants. Teams suggested that other peer assessment systems could work such as rewarding additional or floating marks to high performing team members. CONCLUSIONS: Other models of peer assessment need to be developed and tested that are non-threatening and that facilitate early acceptance of this mode of assessment.

Quality of Surgery in Malawi: Comparison of Patient-Reported Outcomes After Hernia Surgery Between District and Central Hospitals.

BACKGROUND: District hospitals in Africa could meet the essential surgical needs of rural populations. However, evidence on outcomes is needed to justify investment in this option, given that surgery at district hospitals in some African countries is usually undertaken by non-physician clinicians. METHODS: Baseline and 2-3-month follow-up measurements were undertaken on 98 patients who had undergone hernia repairs at four district and two central hospitals in Malawi, using a modified quality-of-life tool. RESULTS: There was no significant difference in outcomes between district and central hospital cases, where a good outcome was defined as no more than one severe and three mild symptoms. Outcomes were marginally inferior at district hospitals (OR 0.79, 95% CI 0.63-1.0). However, in the 46 cases that underwent elective surgery at district hospitals, baseline scores for severe symptoms were worse (mean = 3.5) than in the 23 elective central hospital cases (mean = 2.5), p = 0.004. Also, the mean change (improvement) in symptom score was higher in district versus central hospital cases (3.9 vs. 2.3). CONCLUSION: The study results support the case for investing in district hospital surgery in sub-Saharan Africa to increase access to essential surgical care for rural populations. This could free up specialists to undertake more complex and referred cases and reduce emergency presentations. It will require investments in training and resources for district hospitals and in supervision from higher levels.

Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy.

UNLABELLED: Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1ß release that contributes to neuroinflammation. Using a reporter mouse in which green fluorescent protein is induced in response to the transcription of P2rx7, we show that expression of the receptor is selectively increased in CA1 pyramidal and dentate granule neurons, as well as in microglia in mice that developed epilepsy after intra-amygdala kainic acid-induced status epilepticus. P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy. Cells transcribing P2rx7 in hippocampal slices from epileptic mice displayed enhanced agonist-evoked P2X7 receptor currents, and synaptosomes from these animals showed increased P2X7 receptor levels and altered calcium responses. A 5 d treatment of epileptic mice with systemic injections of the centrally available, potent, and specific P2X7 receptor antagonist JNJ-47965567 (30 mg/kg) significantly reduced spontaneous seizures during continuous video-EEG monitoring that persisted beyond the time of drug presence in the brain. Hippocampal sections from JNJ-47965567-treated animals obtained >5 d after treatment ceased displayed strongly reduced microgliosis and astrogliosis. The present study suggests that targeting the P2X7 receptor has anticonvulsant and possibly disease-modifying effects in experimental epilepsy. SIGNIFICANCE STATEMENT: Temporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor.

Factors influencing trainee doctor emigration in a high income country: a mixed methods study.

BACKGROUND: The Global Code of Practice on the International Recruitment of Health Personnel focuses particularly on migration of doctors from low- and middle-income countries. Less is understood about migration from high-income countries. Recession has impacted several European countries in recent years, and in some cases emigration has reached unprecedented levels. This study measures and explores the predictors of trainee doctor emigration from Ireland. METHODS: Using a partially mixed sequential dominant (quantitative) study design, a nationally representative sample of 893 trainee doctors was invited to complete an online survey. Of the 523 who responded (58.6% response rate), 423 were still in Ireland and responded to questions on factors influencing intention to practice medicine abroad and are the subjects of this study. Explanatory factors for intention to practice medicine in Ireland in the foreseeable future, the primary outcome, included demographic variables and experiences of working within the Irish health system. Associations were examined using univariable and multivariable logistic regression to estimate odds ratios for factors influencing the primary outcome. Qualitative interviews were conducted with 50 trainee doctors and analysed thematically, exploring issues associated with intention to practice medicine abroad. RESULTS: There were high levels of dissatisfaction among trainee doctors around working conditions, training and career progression opportunities in Ireland. However, most factors did not discriminate between intention to leave or stay. Factors that did predict intention to leave included dissatisfaction with one's work-life balance (odds ratio (OR) 2.51; 95% confidence interval (CI) 1.53-4.10; P < 0.001); feeling that the quality of training in Ireland was poor (OR 1.82; 95% CI 1.09-3.05; P = 0.002) and leaving for family or personal reasons (OR 1.85; 95% CI 1.08-3.17; P = 0.027). Qualitative findings illustrated the stress of doing postgraduate training with inadequate supervision, lack of ring-fenced training time and pressures on personal and family life. CONCLUSIONS: Large-scale dissatisfaction with working, training and career opportunities point to systemic factors that need to be addressed by health workforce planners if Ireland is to retain and benefit from a motivated medical workforce, given trainees' perceptions that there are better opportunities abroad.

Medical student INtervention to promote effective nicotine dependence and tobacco HEalthcare (MIND-THE-GAP): single-centre feasibility randomised trial results.

BACKGROUND: Although brief cessation advice from healthcare professionals increases quit rates, smokers typically do not get this advice during hospitalisation, possibly due to resource issues, lack of training and professionals' own attitudes to providing such counselling. Medical students are a potentially untapped resource who could deliver cessation counselling, while upskilling themselves and changing their own attitudes to delivering such advice in the future; however, no studies have investigated this. We aimed to determine if brief student-led counselling could enhance motivation to quit and smoking cessation behaviours among hospitalised patients. METHODS: A mixed-methods, 2-arm pilot feasibility randomised controlled trial with qualitative process evaluation enrolled 67 hospitalised adult smokers, who were recruited and randomized to receive a brief medical student-delivered cessation intervention (n = 33) or usual care (n = 34); 61 medical students received standardised cessation training and 33 were randomly assigned to provide a brief in-hospital consultation and follow-up support by phone or in-person one week post-discharge. Telephone follow-up at 3- and 6-months assessed scores on the Motivation to Stop Smoking Scale (MTSS; primary outcome) and several other outcomes, including 7-day point prevalent abstinence, quit attempts, use of cessation medication, and ratings of student's knowledge and efficacy. Data were analysed as intention to treat (ITT) using penalised imputation, per protocol, and random effects repeated measures. Focus group interviews were conducted with students post-intervention to elicit their views on the training and intervention process. RESULTS: Analyses for primary and most secondary outcomes favoured the intervention group, although results were not statistically significant. Point prevalence abstinence rates were significantly higher for the intervention group during follow-up for all analyses except 6-month ITT analysis. Fidelity was variable. Patients rated students as being "very" knowledgeable about quitting and "somewhat" helpful. Qualitative results showed students were glad to deliver the intervention; were critical of current cessation care; felt constrained by their inability to prescribe cessation medications and wanted to include cessation and other behavioural counselling in their normal history taking. CONCLUSIONS: It appears feasible for medical students to be smoking cessation interventionists during their training, although their fidelity to the intervention requires further investigation. A definitive trial is needed to determine if medical students are effective cessation counsellors and if student-led intervention could be tailored for other health behaviours. TRIAL REGISTRATION: NCT02601599 (retrospectively registered 1 day after first participant recruited on November 3rd 2015).

Distinct behavioral and epileptic phenotype differences in 129/P mice compared to C57BL/6 mice subject to intraamygdala kainic acid-induced status epilepticus.

Animal models of status epilepticus are important tools to understand the pathogenesis of epileptic brain injury and evaluate potential seizure-suppressive, neuroprotective, and antiepileptogenic treatments. Focal elicitation of status epilepticus by intraamygdala kainic acid in mice produces unilateral hippocampal damage and the emergence of spontaneous recurrent seizures after a short latent period. The model has been characterized in C57BL/6, BALB/c, and SJL mice where strain-specific differences were found in the extent of hippocampal damage. 129/P mice are a common background strain for genetic models and may display unique characteristics in this model. We therefore compared responses to intraamygdala kainic acid between 129/P and C57BL/6 mice. Racine scale-scored convulsive behavior during status epilepticus was substantially lower in 129/P mice compared with that in C57BL/6 mice. Analysis of surface-recorded electroencephalogram (EEG) showed differences between strains in several frequency bands; EEG total power was greater during ictal episodes while duration of seizures was slightly shorter in 129/P mice. Histological analysis revealed similar hippocampal injury between strains, with neuronal death mainly confined to the ipsilateral CA3 subfield. Expression of genes associated with gliosis and neuroinflammatory responses was also similar between strains after seizures. Video-EEG telemetry recordings showed that 129/P mice first display spontaneous seizures within a few days of status epilepticus similar to C57BL/6 mice. However, high mortality in 129/P mice prevented a quantitative comparison of the epileptic seizure phenotypes between strains. This study defined behavioral, EEG, and histopathologic features of this mouse strain in a model increasingly useful for the study of the genetic contribution to acquired epilepsy. Intraamygdala kainic acid in 129/P mice could serve as a model of nonconvulsive status epilepticus, but long-term assessments will require model adjustment to mitigate the severity of the emergent epileptic phenotype.

Systematic Review and Individual Patient Data Meta-Analysis of Sex Differences in Depression and Prognosis in Persons With Myocardial Infarction: A MINDMAPS Study.

OBJECTIVE: Using combined individual patient data from prospective studies, we explored sex differences in depression and prognosis post-myocardial infarction (MI) and determined whether disease indices could account for found differences. METHODS: Individual patient data analysis of 10,175 MI patients who completed diagnostic interviews or depression questionnaires from 16 prospective studies from the MINDMAPS study was conducted. Multilevel logistic and Cox regression models were used to determine sex differences in prevalence of depression and sex-specific effects of depression on subsequent outcomes. RESULTS: Combined interview and questionnaire data from observational studies showed that 36% (635/1760) of women and 29% (1575/5526) of men reported elevated levels of depression (age-adjusted odds ratio = 0.68, 95% confidence interval [CI] = 0.60-0.77). The risk for all-cause mortality associated with depression was higher in men (hazard ratio = 1.38, 95% CI = 1.30-1.47) than in women (hazard ratio = 1.22, 95% CI = 1.14-1.31; sex by depression interaction: p < .001). Low left ventricular ejection fraction (LVEF) was associated with higher depression scores in men only (sex by LVEF interaction: B = 0.294, 95% CI = 0.090-0.498), which attenuated the sex difference in the association between depression and prognosis. CONCLUSIONS: The prevalence of depression post-MI was higher in women than in men, but the association between depression and cardiac prognosis was worse for men. LVEF was associated with depression in men only and accounted for the increased risk of all-cause mortality in depressed men versus women, suggesting that depression in men post-MI may, in part, reflect cardiovascular disease severity.

Systematic review and meta-analysis of closed suction drainage versus non-drainage in primary hip arthroplasty.

The routine use of drains in surgery has been dogmatically instituted in some disciplines. Orthopaedic surgery is one such sub-speciality. The use of postoperative closed suction drainage in total hip arthroplasty (THA) has become increasingly controversial with multiple randomised control trials performed to assess the benefit to outcome in THA. The hypothesis of this systematic review is that closed suction drainage does not infer a benefit and increase transfusion requirements of primary total hip arthroplasty patients. A systematic review and meta-analysis was conducted adhering to the PRISMA guidelines. A search of the available literature was performed on PubMed, Cochrane Central Registry of Controlled Trials, MEDLINE (OVID) and EMBASE using a combination of MeSH terms and Boolean operators. All data analysis was performed using the Cochrane Collaboration's Review Manager 5.1. Sixteen studies (n=2705) were included in the analysis. Post-operative closed suction drainage was found to increase total blood loss and blood transfusion requirements (p<0.05). Surgical site infection demonstrated no significant difference between the two groups (p=0.82). No significant difference in haematoma formation between groups (p=0.19) was elicited. The routine use of closed suction drainage systems post primary hip arthroplasty is not supported by this meta-analysis. However, the heterogeneity between studies does limit the accuracy of the meta-analysis.

Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079.

PURPOSE: ATP is an essential transmitter/cotransmitter in neuron function and pathophysiology and has recently emerged as a potential contributor to prolonged seizures (status epilepticus) through the activation of the purinergic ionotropic P2X7 receptor (P2X7R). Increased P2X7R expression has been reported in the hippocampus, and P2X7R antagonists reduced seizure-induced damage to this brain region. However, status epilepticus also produces damage to the neocortex. The present study was designed to characterize P2X7R in the neocortex and assess effects of P2X7R antagonists on cortical injury after status epilepticus. METHODS: Status epilepticus was induced in mice by intraamygdala microinjection of kainic acid. Specific P2X7R inhibitors were administered into the ventricle before seizure induction, and cortical electroencephalography and behavior was recorded to assess seizure severity. P2X7R expression was examined in neocortex up to 24 h after status epilepticus, in epileptic mice, and in resected neocortex from patients with pharmacoresistent temporal lobe epilepsy (TLE). In addition, the induction of P2X7R after status epilepticus was investigated using transgenic P2X7R reporter mice, which express enhanced green fluorescent protein under the control of the p2x7r promoter. KEY FINDINGS: Status epilepticus resulted in increased P2X7R protein levels in the neocortex of mice. Neocortical P2X7 receptor levels were also elevated in mice that developed epilepsy after status epilepticus and in resected neocortex from patients with pharmacoresistent TLE. Immunohistochemistry determined that neurons were the major cell population transcribing the P2X7R in the neocortex within the first 8 h after status epilepticus, whereas in epileptic mice, P2X7R up-regulation occurred in microglia as well as in neurons. Pretreatment of mice with the specific P2X7R inhibitor A-438079 reduced electrographic and clinical seizure severity during status epilepticus and reduced seizure-induced neuronal death in the neocortex. SIGNIFICANCE: Our findings identify neurons in the neocortex as an important site of P2X7R up-regulation after status epilepticus and in epilepsy, and provide support for the possible use of P2X7R antagonists for the treatment of status epilepticus and prevention of seizure-induced brain damage.

A genome-wide association study of recipient genotype and medium-term kidney allograft function.

BACKGROUND: We examined, through genome-wide association studies (GWAS), the correlation between recipient genetic variation and renal function at five yr. METHODS: Our cohort contained 326 Irish, first time, kidney-only, deceased donor, transplant recipients on calcineurin inhibitors (263 had a functioning graft at five yr) between 1993 and 2002. Outcomes were creatinine at five yr and long-term graft function. RESULTS: Two variants were identified showing borderline genome-wide significance - one on chromosome 18 (p = 4.048e-08, rs6565887) and another on chromosome 14 (p = 7.631e-08, rs3811321). Individually, the two SNPs explained up to 8.8% and 11.29% of five-yr creatinine variance, respectively, while together they explained up to 17.4% of trait variance. Both variants were predictors of long-term allograft function (p = 0.004, 70% vs 30% survival at 10 yr). The chromosome 14 variant is located in the intergenic region of the T-Cell Receptor Alpha locus. CONCLUSIONS: Using a genome-wide approach, we have identified two associations with five-yr creatinine levels in renal transplant recipients treated with calcineurin inhibitors. Independent replication is now warranted to clarify the clinical significance of these results.

What's distressing about having type 1 diabetes? A qualitative study of young adults' perspectives.

BACKGROUND: Diabetes distress is a general term that refers to the emotional burdens, anxieties, frustrations, stressors and worries that stem from managing a severe, complex condition like Type 1 diabetes. To date there has been limited research on diabetes-related distress in younger people with Type 1 diabetes. This qualitative study aimed to identify causes of diabetes distress in a sample of young adults with Type 1 diabetes. METHODS: Semi-structured interviews with 35 individuals with Type 1 diabetes (23-30 years of age). RESULTS: This study found diabetes related-distress to be common in a sample of young adults with Type 1 diabetes in the second phase of young adulthood (23-30 years of age). Diabetes distress was triggered by multiple factors, the most common of which were: self-consciousness/stigma, day-to-day diabetes management difficulties, having to fight the healthcare system, concerns about the future and apprehension about pregnancy. A number of factors appeared to moderate distress in this group, including having opportunities to talk to healthcare professionals, attending diabetes education programmes and joining peer support groups. Young adults felt that having opportunities to talk to healthcare professionals about diabetes distress should be a component of standard diabetes care. CONCLUSIONS: Some aspects of living with diabetes frequently distress young adults with Type 1 diabetes who are in their twenties. Clinicians should facilitate young adults' attendance at diabetes education programmes, provide them with opportunities to talk about their diabetes-related frustrations and difficulties and, where possible, assist in the development of peer-support networks for young adults with diabetes.