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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.

ObjectivesTo quantify the prevalence and nature of adverse events in acute Irish hospitals in 2015 and to assess the impact of the National Clinical Programmes and the National Clinical Guidelines on the prevalence of adverse events by comparing these results with the previously published data from 2009.Design and methodsA retrospective chart review of 1605 admissions to eight Irish hospitals in 2015, using identical methods to those used in 2009.ResultsThe percentage of admissions associated with one or more adverse events was unchanged (p=0.48) at 14% (95% CI=10.4% to 18.4%) in 2015 compared with 12.2% (95% CI=9.5% to 15.5%) in 2009. Similarly, the prevalence of preventable adverse events was unchanged (p=0.3) at 7.4% (95% CI=5.3% to 10.5%) in 2015 compared with 9.1% (95% CI=6.9% to 11.9%) in 2009. The incidence densities of preventable adverse events were 5.6 adverse events per 100 admissions (95% CI=3.4 to 8.0) in 2015 and 7.7 adverse events per 100 admissions (95% CI=5.8 to 9.6) in 2009 (p=0.23). However, the percentage of preventable adverse events due to hospital-associated infections decreased to 22.2% (95% CI=15.2% to 31.1%) in 2015 from 33.1% (95% CI=25.6% to 41.6%) in 2009 (p=0.01).ConclusionAdverse event rates remained stable between 2009 and 2015. The percentage of preventable adverse events related to hospital-associated infection decreased, which may represent a positive impact of the related national programmes and guidelines.

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.

Background Adverse events are any injuries caused by healthcare management, which result in disability, increased length of stay or death. The Irish National Adverse Event Study (INAES)(1) used the Harvard Medical Practice, 2-step methodology of retrospective chart review(2) to determine the adverse event rate in the Irish inpatient cohort. Methods We further analysed the INAES data in order to calculate the prevalence and determine the impact of adverse events on the older inpatient population. Results INAES captured 1574 randomly selected adult inpatient admissions from 8 hospitals across the Republic of Ireland in 2009. 53% were female and the median age was 55years (IQR 37years to 72years). The prevalence of adverse events was higher in those aged ≥65 compared to those aged < 65 (15.4% versus 9.3% P < 0.001). When an adverse event did occur it was more likely to result in death in the ≥65 years old group (11.4% versus 2.1%, p = 0.01). Furthermore, it was 9 times more likely that an admission would result in a fatal adverse event in those aged ≥65 compared to those aged < 65 years. A further 9% of adverse events in the ≥65 age group resulted in permanent disability and over half were thought to be preventable. Older patients who suffered from an adverse event had an increased length of stay compared to older patients who did not suffer an adverse event (16days versus 6days, p Conclusion Older inpatients are more likely to suffer from an adverse event than their younger counterparts. These adverse events are more likely to contribute to increased morbidity but over half are preventable. The follow-up INAES-2 study, which is currently underway, will determine if an improvement has been made after implementation of the National Clinical Programmes.

Summary Background Point prevalence surveys (PPSs) collect data on hospital-acquired infections (HAIs) at one point in time but do not provide information on incidence over the entire admission or impact on patients or healthcare resources. Retrospective record review examines the entire admission to determine adverse event prevalence, incidence, preventability, physical impairment and additional length of stay. Aim To establish whether European HAI surveillance definitions can be applied to the Irish National Adverse Events Study (INAES) retrospective record review data to determine HAI burden. Methods In the INAES, 1574 admissions were reviewed using a two-stage methodology and 247 adverse events were found. These were examined against European HAI case definitions to determine whether the event was an HAI. Results were compared with the 2011/12 European PPS data for Ireland. Findings The prevalence of HAI adverse events in INAES was 4.4% (95% confidence interval (CI) 3.1–6.1%) with an incidence of 3.8 (95% CI 2.5–5.2) HAI adverse events per 100 admissions. The PPS HAI prevalence for Ireland was 5.2%. HAI types and micro-organisms were similar in INAES and the PPS. Approximately three-quarters of INAES HAI adverse events were preventable, 7% caused permanent impairment and 7% contributed to death. A mean of 10 additional bed days were attributed to HAI adverse events, equivalent to €9400 per event. Conclusion Retrospective record review is an accurate source of information on HAI incidence, preventability and impact that complements PPS prevalence rates. HAI adverse events result in higher costs to the healthcare system than other adverse events.

Convalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

Supplemental digital content is available in the text., Objective This study aimed to determine if the implementation of large-scale patient safety initiatives have been successful in reducing overall and preventable adverse event rates in hospital inpatients. Design The design used in this study was systematic review and meta-analysis. Data Resources We followed our published protocol (PROSPERO [CRD42019140058]) and searched the following databases: PubMed, CINAHL, PsycINFO, Cochrane Library, and Embase from inception to February 2020. The reference lists of eligible studies were also searched. Eligibility All longitudinal retrospective record review studies that examined adverse event rates before and after the introduction of patient safety initiatives in hospital inpatients were included. Data Extraction Data extraction, quality, and risk of bias assessment were carried out by 2 independent reviewers. Information on study design, setting, demographics, interventions, and safety outcome measures was extracted. Results A total of 3894 articles were screened, and 7 articles met the eligibility criteria for our systematic review with 5 of these providing sufficient information for inclusion in the meta-analysis. The degree of heterogeneity was high among studies. The meta-analysis demonstrated a minimal risk reduction in overall adverse event rates of 0.017 (95% confidence interval, 0.002–0.032) when the lower-quality studies were excluded, with one adverse event being prevented for every 59 hospital admissions. Conclusions These findings are significant when the large numbers of admissions to a hospital every year are considered. Given the low numbers of large-scale implementation studies, there is a need for more research on the effectiveness of patient safety initiatives to further assess the impact of such initiatives on adverse events.

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.

BackgroundConvalescent plasma (CP) therapy in COVID-19 disease has been suggested to improve clinical outcome in severe disease. This pilot study was designed to inform the design of a definitive phase 3 clinical trial.MethodsThis was a prospective, interventional and randomized open label pilot trial involving 40 patients with COVID-19 who were requiring oxygen therapy and who had radiological evidence of pneumonia. Twenty COVID-19 patients received two 200ml transfusions of convalescent patient CP over 24 hours were compared with 20 patients who received routine care alone. The primary outcome was the requirement for ventilation. The secondary outcomes were white blood cell count, lactate dehydrogenase (LDH), C-reactive protein (CRP), Troponin, Ferritin, D-Dimer, procalcitonin, mortality rate at 28 days.ResultsThe CP group were a higher risk group with higher ferritin levels (pConclusionThere were no significant differences in the primary or secondary outcome measures between CP and standard therapy though fewer patients required ventilation and for a shorter period of time. The study showed that CP therapy appears to be safe and it is feasible to perform a definitive phase 3 clinical trial using this study protocol.

Objectives Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale – depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. Methods We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. Results 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was −21.1% to 19.5%. Conclusions HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed, however, an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.

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.

Objective Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Methods Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores. Results There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)). Conclusion Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.

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.

BackgroundIntestinal parasitic infections (IPIs) and anaemia are major health problems. This study assessed the prevalence of IPI, anaemia and associated factors among pre-school children in rural areas of the Tigray region, northern Ethiopia.Methodology/Principal FindingA 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. Among the 610 pre-school children participated in the study, prevalence of IPIs and anaemia were 58% (95% CI: 54.1–61.9%) and 21·6% (95% CI: 18·5% to 25·1%), respectively. Single, double, and triple parasitic infections were seen in 249 (41%, 95% CI: 37% to 45%), 83 (14%, 95% CI: 11% to 17%), and 22 (3.6%, 95% CI: 2.4% to 5.4%) children, respectively. Of the seven intestinal parasitic organisms recorded from the participants,Entamoeba histolytica/disparwas the most prevalent 220 (36.1%) followed byGiardia lamblia128 (20.1%), andHymenolepis nana102 (16.7%). Mixed infections were common amongG. lamblia, E. histolytica/disparandCryptosporidiumspp. oocyst. Age 48-59 months prevalence ratio (PR = 1·078, P=0·009), child deworming (PR= 1.2; 95% CI=1.00-1.4, p= 0.045), and having two or more children aged under five (PR=0.76, 95% CI= 0.61-0.95, p=0.015) were independent predictors for IPIs. Anaemia was associated with proper disposal of solid waste (PR= 1.5, 95% CI=0.1.1-2.10, p=0.009). 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.ConclusionsMore than half of the children were infected with intestinal parasites and one in five were anaemic. 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.Author SummaryIntestinal parasitic infection and anaemia are public health problems in developing counties. Children due to their immature immune systems and frequent exposure to unhygienic environments are at high risk which in turn put them at an increased risk of malnutrition and growth deficits. Similarly, childhood anaemia impairs physical growth, impairs immune function and weakens motor development. The finding of this study reveals more than half of the children were infected.Entamoeba histolytica/dispar, Giardia lambliaandHymenolepis nanawere dominant parasites. Multiple infections was common amongGiardia lamblia, Entamoeba histolytica/disparandCryptosporidiumspp. Oocyst. Children aged 48-59 months were more infected with intestinal parasites. Soli transmitted helminths in this study was low. 21.5% of the children were anaemic and was associated with disposal of solid waste and presence of domestic animals. However, Eating raw meat, maternal education and household water treatment were found preventive of anaemia in the study. It seems worth understanding the prevalence and effects of parasitic infection and anaemia in this vulnerable group to design an appropriate interventions. Finally, if parasite transmission and anaemia is to be significantly prevented control programs such as improving sanitation, clean water, maternal education may be critical in this vulnerable age groups.

Contains fulltext : 214941.pdf (Publisher’s version ) (Open Access) We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository. 3 p.

Author(s): Aczel, Balazs; Szaszi, Barnabas; Sarafoglou, Alexandra; Kekecs, Zoltan; Kucharský, Simon; Benjamin, Daniel; Chambers, Christopher D; Fisher, Agneta; Gelman, Andrew; Gernsbacher, Morton A; Ioannidis, John P; Johnson, Eric; Jonas, Kai; Kousta, Stavroula; Lilienfeld, Scott O; Lindsay, D Stephen; Morey, Candice C; Munafo, Marcus; Newell, Benjamin R; Pashler, Harold; Shanks, David R; Simons, Daniel J; Wicherts, Jelte M; Albarracin, Dolores; Anderson, Nicole D; Antonakis, John; Arkes, Hal R; Back, Mitja D; Banks, George C; Beevers, Christopher; Bennett, Andrew A; Bleidorn, Wiebke; Boyer, Ty W; Cacciari, Cristina; Carter, Alice S; Cesario, Joseph; Clifton, Charles; Conroy, Ronan M; Cortese, Mike; Cosci, Fiammetta; Cowan, Nelson; Crawford, Jarret; Crone, Eveline A; Curtin, John; Engle, Randall; Farrell, Simon; Fearon, Pasco; Fichman, Mark; Frankenhuis, Willem; Freund, Alexandra M; Gaskell, M Gareth; Giner-Sorolla, Roger; Green, Don P; Greene, Robert L; Harlow, Lisa L; de la Guardia, Fernando Hoces; Isaacowitz, Derek; Kolodner, Janet; Lieberman, Debra; Logan, Gordon D; Mendes, Wendy B; Moersdorf, Lea; Nyhan, Brendan; Pollack, Jeffrey; Sullivan, Christopher; Vazire, Simine; Wagenmakers, Eric-Jan | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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. 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. 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). 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.

BackgroundRapid access to thrombectomy for patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) is critical for improving outcome. A major challenge for the ‘drip and ship’ model is reducing the door-in-door-out time (DIDO). We propose a new protocol with the aim of reducing DIDO, without adversely affecting emergency service usage time.MethodsConsecutive patients with suspected LVO AIS admitted to a Primary Stroke Center (PSC) from October 2018 to January 2021 were included. On arrival, the ambulance crew remained with the patient. Following immediate clinical and radiological evaluation, patients were transferred to the Comprehensive Stroke Center (CSC) by the same waiting crew. Key time metrics were collected and compared with historical data prior to the new protocol.Results27 patients had an LVO amenable for mechanical thrombectomy during the time period. There was a significant reduction in the DIDO times compared with the historical group (median 45 min vs 96 min; pConclusionOur data show a significant reduction in the DIDO for patients transferred for thrombectomy, with no adverse effects on ambulance usage time.

Neonatal seizures are a common consequence of hypoxic/ischemic encephalopathy (HIE). Phenobarbital remains the frontline treatment for neonatal seizures but is often ineffective. The P2X7 receptor (P2X7R) is a cell surface-expressed ionotropic receptor activated by high amounts of ATP which may be released during seizures or as a consequence of tissue injury. Here, we explored the role of the P2X7R in a mouse model of neonatal seizures induced by hypoxia. Exposure of postnatal day 7 (P7) mouse pups to global hypoxia (5% O2 for 15 min) produced electrographically-defined seizures with behavioural correlates that persisted after restitution of normoxia. Expression of the P2X7R showed age-dependent increases in the hippocampus and neocortex of developing mice and was present in human neonatal brain. P2X7R transcript and protein levels were increased 24 h after neonatal hypoxia-induced seizures in mouse pups. EEG recordings in pups determined that injection of the P2X7R antagonist A-438079 (25 mg/kg−1, intraperitoneal) reduced electrographic seizure number, EEG power and spiking during hypoxia. A-438079 did not reduce post-hypoxia seizures. Caspase-1 processing and molecular markers of inflammation and microglia were reduced in A438079-treated mice. Electrographic seizure-suppressive effects were also observed with a second P2X7R antagonist, JNJ-47965567, in the same model. The present study shows hypoxia-induced seizures alter expression of purinergic and neuroinflammatory signalling components and suggest potential applications but also limitations of the P2X7R as a target for the treatment of HIE and other causes of neonatal seizures.

Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus. Translation of these findings would benefit from evidence of efficacy in non-status epilepticus models and validation in another species. Here, we report that electrographic seizures and convulsive behavior are strongly reduced in adult mice pre-treated with Ant-134 in the pentylenetetrazol model. Pre-treatment with Ant-134 did not affect the severity of status epilepticus induced by perforant pathway stimulation in adult rats, a toxin-free model of acquired epilepsy. Nevertheless, Ant-134 post-treatment reduced the number of rats developing spontaneous seizures by 86% in the perforant pathway stimulation model and Ant-134 delayed epileptiform activity in a rat ex vivo hippocampal slice model. The potent anticonvulsant effects of Ant-134 in multiple models may encourage pre-clinical development of this approach to epilepsy therapy. Keywords: noncoding RNA, hippocampal sclerosis, epileptogenesis, chemoconvulsant, status epilepticus, anti-epileptic drug, temporal lobe epilepsy

BackgroundMedical 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”.MethodsA 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.ResultsThe 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.ConclusionsOther models of peer assessment need to be developed and tested that are non-threatening and that facilitate early acceptance of this mode of assessment.

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.

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 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.

ObjectivesThis cross-sectional study was designed to measure burnout and its impact on risk of depression in a medical student population, comparing the preclinical and clinical years.DesignWe conducted a survey of 269 medical school students in both preclinical and clinical years at the Royal College of Surgeons in Ireland, using the Beck Depression Inventory-Fast Screen (BDI-FS), the Maslach Burnout Inventory-Student Survey and items assessing willingness to use mental health services. Burnout scores were calibrated to probability of depression caseness and classified as low risk (50%) of depression.ResultsThere was a 39% (95% CI 33% to 45%) prevalence of depressive caseness based on a score of ≥6 on the BDI-FS. Prevalence did not vary significantly between clinical and preclinical years. The rate of burnout varied significantly between years (p=0.032), with 35% in the high-burnout category in clinical years compared with 26% in preclinical years. Those in the low burnout category had a 13% overall prevalence of depressive symptoms, those in the intermediate category had a 38% prevalence and those in the high category had a 66% prevalence of depressive symptoms. Increasing emotional exhaustion (OR for one—tertile increase in score 2.0, p=0.011) and decreasing academic efficacy (OR 2.1, p=0.007) increased the odds of being unwilling to seek help for mental health problems (11%).ConclusionWhile previous studies have reported significant levels of burnout and depression, our method of calibrating burnout against depression allows burnout scores to be interpreted in terms of their impact on mental health. The high prevalences, in line with previous research, point to an urgent need to rethink the psychological pressures of health professions education.

Introduction Irish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence. Objective To assess the frequency and nature of adverse events in Irish hospitals. Methods 1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined. Results 45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to-moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of (sic)5550 per event. The adverse event rate varied substantially (8.6%-17.0%) when applying different published adverse event eligibility criteria. Conclusions This first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over (sic)194 million. These results provide important baseline data on the adverse event burden and, alongside web-based chart review, provide an incentive and methodology to monitor future patient-safety initiatives.

Background: Hospitalisation is an ideal time to implement smoking cessation interventions. However, little is known about the extent to which inpatients receive such advice, or the impact it has on motivation to quit and quitting behaviours post-hospitalisation. Aims: This study aimed to determine the prevalence of smoking and cessation advice received by inpatients in two teaching hospitals in Ireland, and the impact of cessation advice on smoking at 3 months post discharge. Methods: We surveyed 1001 inpatients across two hospital sites, over a six-month period. Demographic details, clinical history, smoking history, motivation to quit, cigarette dependence, and recent quitting history were assessed. Results: Prevalence of smoking within the sample was 23.4% (235/1001). Only 32% (75/235) of smokers reported that smoking cessation was discussed during admission. Smokers’ mean Fagerström nicotine-dependence score was 3.7 (SD = 2.7), indicating low dependence levels. At 3 months, 17% (25/146) of smokers reported smoking cessation. Provision of smoking cessation advice during hospitalisation was associated with higher motivation to quit (OR = 2.79, 95% CI 2.12–3.68), and successful quit behaviour for confirmed (OR = 1.98, 95% CI 1.55–2.53) and self-reported quitters (OR = 1.47, 95% CI 1.3–1.66) Conclusions: This observational study finds that provision of brief cessation advice and smoking status documentation was suboptimal. Where advice was given, it was associated with enhanced motivation to quit and increased quit rates. These findings, along with low dependence scores, suggest that systematic provision of low-intensity cessation interventions could significantly enhance quit rates in hospitalised smokers.

Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important tool in the management of advanced germ cell testis cancer, particularly non-seminoma. We present the 16-year experience with PC-RPLND in a single Irish tertiary referral centre, and compare our results to the major speciality centres worldwide. All 78 patients undergoing PC-RPLND for the treatment of metastatic testis cancer between January 1996 and December 2011 were included. Medical records were reviewed and up to date follow-up obtained from primary referral centres, patient’s GPs and individual patient interview. The mean age at diagnosis was 28.5 ± 7 years. Initial pathology included non-seminoma 62.8 %, seminoma 6.4 % and combined 19.2 %. All patients underwent pre-operative chemotherapy. The resection template utilised was bilateral infra-hilar in 29.5 %, unilateral infra-hilar in 46.2 % and supra-hilar in 20.5 %. Complete abdominal remission was achieved in all but one patient. Additional procedures were required in 38.5 % of patients (n = 30). Clavien Dindo grade three or four complications were seen in 8.9 %, including five patients who required early reoperation. Histology of RPLND specimen showed mature teratoma (41 %) and active cancer (11.5 %). Follow-up data were available for 66 patients (85 %). Median follow-up was 101 (11–207) months. Nine patients relapsed with median time to relapse 15 (8–60) months. Overall 5-year survival rate was 95.2 % (four deaths). In this relatively small series due to small population and low disease incidence, we have shown acceptable peri-operative course, morbidity and oncological outcomes with PC-RPLND compared to major international centres.

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.

Objectives: Depression and vital exhaustion are associated with poor cardiovascular prognosis, but there is substantial overlap between these constructs. Factor analytic studies have been inconclusive, and may not be the optimal analytic strategy to assess dimensionality. We assessed whether exhaustion and depression formed a single, hierarchical dimension using a form of nonparametric item response theory.Methods: Patients with acute coronary syndrome (n = 430) completed questionnaires assessing depression and vital exhaustion. Mokken scaling was used to assess dimensionality.Results: Mokken scaling formed a strong unidimensional scale, ordered in a hierarchy reflecting prevalence: fatigue (common), depression (less common) and hopelessness (rare).Conclusions: Depressive symptoms form a clear hierarchy in cardiac patients, from fatigue to hopelessness. Vital exhaustion may be considered a less severe form of depression. Use of hierarchical scales may allow clinicians to better determine clinical significance and target interventions.

Introduction Inability to identify stroke warning signs accurately is an important cause of delay in seeking medical attention, leading to potential ineligibility for acute intervention. We report on post-campaign findings (wave 2) of national surveys to estimate changes in population knowledge following a media-based Face, Arm, Speech, Time stroke awareness campaign, comparing findings to those of a pre-campaign population survey (wave 1). Participants and methods: One thousand and ten randomly selected adults (18+) completed the Stroke Awareness Questionnaire on knowledge of warning signs, risk factors and response to stroke at wave 2 and findings were compared to wave 1 survey results. Logistic regression was used to examine the association between demographic characteristics and self-reported risk factors with knowledge of stroke and emergency response. Results No significant differences existed in the ability of respondents to define stroke or to identify two or more stroke risk factors between waves 1 and 2 surveys (71% and 70%, respectively). Respondents to the wave 2 survey were five times more likely (odds ratio 4.9, p Discussion Although significant improvements were made in several areas of stroke knowledge and intended response, awareness of acute stroke interventions was poor and intended behavioural response was suboptimal. Conclusion Findings from this study indicate need for targeted campaigns to improve population understanding of the reasons underlying the importance of rapid emergency response to stroke.

Objective We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health. Methods The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016. Results The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34–0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48–0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence. Conclusions The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients’ own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.

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.

We investigated health anxiety and attitudes to doctors and medicine as determinants of use of 'alternative' practitioners and treatments in a sample of 200 general practice attenders. The Health Anxiety Questionnaire and the Attitudes to Doctors and Medicine Scale were used, as well as a schedule of non-medical practitioners and treatments. Half those interviewed had ever used diet supplements, and about a quarter had ever used other nonmedical treatments such as herbal remedies and mega vitamins. 20% has been to a massage therapist, roughly 10% to a faith healer, acupuncturist or chiropractor. Health anxiety scores were unrelated to consultations except that those who had visited a faith healer or had taken dietary supplements were significantly more anxious. On the other hand, positive attitudes to doctors and medicine were positively correlated with almost all measures of use of alternative treatments. Rather than being a rejection of scientific medicine, it suggests that 'alternative' medicine is not distinguished from scientific medicine by Dublin GP attenders.

Objective To investigate whether scores on a psychological measure of concentration and interpersonal characteristics, The Attentional and Interpersonal Style Inventory (TAIS), are associated with performance of surgical skills. Design Postgraduate surgical trainees completed an operative surgical skills assessment in the simulation laboratory and the psychological measure (TAIS). The surgical skills assessment consisted of 6 tasks (3 per trainee): laceration suturing; lipoma excision; incision and closure of a laparotomy wound; bowel anastomosis; saphenofemoral junction ligation and basic laparoscopic skills. The association between operative surgical skill performance and TAIS factors was investigated. Setting The TAIS assessments and surgical skills assessments were conducted at the National Surgical Training Centre at the Royal College of Surgeons in Ireland (RCSI). Participants One hundred and two surgical trainees in years one and two (PGY 2-3 equivalent) participated in the study. Results Performance on 2 of the 6 tasks assessed (bowel anastomosis and lipoma excision) were positively associated with multiple TAIS factors (energy, confidence, competitiveness, extroversion, self-criticism and performing under pressure). Another factor, focus over time, was significantly associated with scores on the lipoma excision task. Conclusions Trainees with high levels of energy, confidence, competitiveness, extroversion, and focus over time and low levels of self-criticism demonstrated better performance on specific technical skills tasks.

Background. Depression is an increasing problem in older adults, which is exacerbated by under diagnosis and ineffective treatment options. Broadly speaking, as people age, their levels of regular physical activity (PA) decrease, while their experience of chronic pain increases. PA has been shown to be an effective, yet under-utilised, treatment for depression in this age-cohort although the influence of pain on the relationship between PA and depressive symptoms has not been considered. Methods. Secondary analysis of national data from The Irish Longitudinal Study on Ageing (TILDA, 2011) (n = 8163 participants aged 50 years and older) examined the mediating or moderating role of pain in the relationship between depressive symptoms and PA, and the impact of PA, pain and depressive symptoms on health-care utilisation. Results. Approximately 8.5% TILDA older adults were depressed. No mediating or moderating effects of pain were found in the association between PA and depressive symptoms. Higher levels of PA were found to be independently associated with lower depressive symptoms, while higher levels of pain significantly increased the likelihood of depressive symptoms supporting previous findings. Depressive symptoms and higher levels of pain were also found to significantly increase health-care utilisation. Conclusions. Consistent with previous findings in this field, both PA and pain were found to be independently associated with depressive symptoms in Irish older adults. Furthermore, pain does not play a mediating or moderating role in the relationship between PA and depressive symptoms. Continued support for ongoing initiatives in this area aimed at increasing PA in older adults as a means to improve both physical and mental well-being is advised. The absence of any synergistic effect between PA and pain suggests that clinicians and health service providers should continue to promote PA as a treatment for depression, irrespective of the pain levels of their patients.

Background/Aim Estimating the measurement error (reliability) of three dimensional gait analysis (3DGA) is crucial to interpretation of gait data. The purpose of this study was to investigate the intra-rater reliability of 3DGA and apply a novel method of visualising reliability of gait cycle waveforms. Methods A test re-test design was employed. A convenience sample of 30 healthy adults (18F; 12M: mean age 30 ± 6.8 years) participated. Subjects walked along a 10 m walkway at their preferred gait speed and 3DGA data were collected using a VICON ® 3DGA system. Testing was performed by the same investigator on two separate days within two weeks. Data from 10 trials were averaged and analysed. Analysis The intraclass correlation coefficient (ICC), the standard error of measurement (SEM), minimal detectable change (MDC) and limits of agreement were calculated for kinetic and kinematic data. Bland and Altman plots were applied to gait cycle waveforms. Results Spatio-temporal parameters such as cadence, step length, velocity, step time and step width were highly repeatable generating ICC's of 0.90 and above and low SEM/MDC. Range of joint movement across the gait cycle was generally more reliable than either minimum or maximum values and higher ICCs were obtained for movement in the sagittal plane. For kinematic data the standard error of measurement was low (≤5) for the majority of parameters. Transverse plane measurements showed poor reliablility with lowest ICC's. ICCs for kinetic data ranged from 0.51 to 0.81. Conclusions Reliability of 3DGA has been estimated for our gait laboratory. Bland and Altman plots of gait cycle waveforms provide a useful addition to reliability analysis.

The attainment of technical competence for surgical procedures is fundamental to a proficiency-based surgical training program. We hypothesized that aptitude may directly affect one's ability to successfully complete the learning curve for minimally invasive procedures. The aim was to assess whether aptitude has an impact on ability to achieve proficiency in completing a simulated minimally invasive surgical procedure. The index procedure chosen was a laparoscopic appendectomy.Two groups of medical students with disparate aptitude were selected. Aptitude (visual-spatial, depth perception, and psychomotor ability) was measured by previously validated tests. Indicators of technical proficiency for laparoscopic appendectomy were established by trained surgeons with an individual case volume of more than 150. All subjects were tested consecutively on the ProMIS III (Haptica) until they reached predefined proficiency in this procedure. Simulator metrics, critical error scores, and Objective Structured Assessment of Technical Skills (OSATS) scores were recorded.The mean numbers of attempts to achieve proficiency in performing a laparoscopic appendectomy for group A (high aptitude) and B (low aptitude) were 6 (range 4 to 7) and 14 (range 10 to 18), respectively (p0.0001). Significant differences were found between the 2 groups for path length (p = 0.014), error score (p = 0.021), and OSATS score (p0.0001) at the initial attempt.High aptitude is directly related to a rapid attainment of proficiency. These findings suggest that resource allocation for proficiency-based technical training in surgery may need to be tailored according to a trainee's natural ability.

Summary 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.

Aims and objectives To examine the weight loss concerns of young adults with type 1 diabetes. Background Eating disorders are prevalent in young women with type 1 diabetes. Design Qualitative. Methods Interviews with 35 young adults (23–30 years of age) with type 1 diabetes and 13 healthcare professionals. Results Most female interviewees were concerned about the difficulties of losing weight when having diabetes. Six female interviewees developed severe eating disturbances when they were younger. These women initially regarded their disturbed eating behaviour positively and engaged in weight loss activities intermittently. However, over time, they lost control of their behaviour, and it came to dominate their lives. Family conflict often intensified disordered eating behaviours. Eventually all of these women managed to transition away from their behaviour, although this process took, for some of them, several years. Several of them (now in their early to late twenties), however, continued to struggle with weight loss impulses. Healthcare professionals felt that eating- and weight-related issues often went undiagnosed and undocumented in young adult women with type 1 diabetes. Conclusion Many young women with type 1 diabetes are worried about their weight, but will not engage in risky weight loss activities because of concerns about their health. A minority of young adult women will develop more severe eating-related disturbances. These eating disturbances may last a significant amount of time before clinicians become aware of them. These women may also experience disordered weight loss impulses for sometime after clinical interventions. Relevance to clinical practice Clinicians should screen young adult women with type 1 diabetes for eating disorders and monitor young adult women who have developed eating disorders over the longer term. There may be a need to provide asymptomatic young women with diabetes with information about the potential risks of insulin omission.

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.

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation. © 2012 Nature America, Inc. All rights reserved.

In this article, I discuss measures of effect size for two-group comparisons where data are not appropriately analyzed by least-squares methods. The Mann–Whitney test calculates a statistic that is a very useful measure of effect size, particularly suited to situations in which differences are measured on scales that either are ordinal or use arbitrary scale units. Both the difference in medians and the median difference between groups are also useful measures of effect size.

Please cite this paper as: Khalid S, Dimitriou E, Conroy R, Paraskevaidis E, Kyrgiou M, Harrity C, Arbyn M, Prendiville W. The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity. BJOG 2012;119:685–691. Objective The aim of this study was to determine if the individual physical characteristics of the extirpated transformation zone after large loop excision of the transformation zone (LLETZ) might predict the relative risk of adverse obstetric outcome, specifically preterm labour (PTL). Design A retrospective observational study. Setting University teaching hospital in Dublin (Coombe Women & Infants University Hospital, CWIUH). Population Women who had LLETZ treatment for cervical intraepithelial neoplasia (CIN) in the colposcopy service between 1999 and 2002, and who subsequently had a pregnancy at the CWIUH. Methods Case records and histology reports for eligible women were examined. Age, parity, smoking history, pregnancy complications and CIN grade were recorded. Exclusion criteria were age >42 years, previous treatment for CIN, previous premature labour or twin pregnancies. The Student’s t-test, Mann–Whitney U-test, analysis of variants (ANOVA) and logistic regression were employed to analyse the data. Main outcome measures Gestational age at birth, PTL (i.e.