Using Real-world Data to Define a Validated Nomogram for Advanced Bladder Cancer Patients Who Respond to Immunotherapy.

AIMS: Immune checkpoint inhibitors (ICIs) are used in incurable urothelial cancers, both in chemo-naïve and platinum-refractory patients. Efficacy and toxicity data published outside controlled clinical trials are limited. We report overall survival, progression-free survival and toxicities of ICIs in locally advanced (LABC) or metastatic bladder cancer (MBC). We aimed to develop and validate a prognostic model for these patients. MATERIALS AND METHODS: A multicentre real-world individual patient-level data study (n = 272) evaluating ICIs in the first-line platinum-ineligible or platinum-refractory setting for LABC/MBC between March 2017 and February 2020 was undertaken. Cox regression analyses evaluated the association of prognostic factors with overall survival. Data were split to create a training (n = 208) and validation (n = 64) cohort. The backward elimination method with a P-value cut-off of 0.05 was used to develop a reduced prognostic model using the training data set. The concordance index and assessment of observed versus predicted survival probabilities were used to evaluate the final model. RESULTS: The median follow-up was 18.9 (15.8-21.5) months. The median overall survival and progression-free survival in the training cohort were 9.2 (95% confidence interval 7.4-10.5) and 4.5 months (3.5-5.7), respectively. The most common grade 1/2 adverse events recorded were fatigue (47.8%) and infection (19.9%). Five key prognostic factors found in the training set were low haemoglobin, high neutrophil count, choice of immunotherapy favouring pembrolizumab, presence of liver metastasis and steroid use within 30 days of treatment. The concordance index for the training and validation cohorts was 0.66 (standard error = 0.05) and 0.64 (standard error = 0.04), respectively, for the final model. A nomogram was developed to calculate the expected survival probabilities based on risk factors. CONCLUSIONS: Real-world data were used to produce a validated prognostic model for overall survival in LABC/MBC treated with ICIs. This model could assist in patient stratification, interpreting and framing future trials incorporating PD-1/PD-L1 inhibitors in LABC/MBC.

Identifying hospital-acquired infections using retrospective record review from the Irish National Adverse Events Study (INAES) and European point prevalence survey case definitions.

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.

A national survey of current practices of preparation and management of radical prostate radiotherapy patients during treatment.

AIMS: Radiotherapy is an important radical treatment for prostate cancer patients with services continually evolving. This survey aims to gain an insight in to the variation of radiotherapy practices in the UK, focussing on pre-treatment preparations, on-treatment review and management of radical prostate cancer patients undergoing radiotherapy. To our knowledge this is the first survey reported focussing on prostate radiotherapy practices with responses from a mix of health professionals. MATERIALS AND METHODS: A national survey was designed based on current known practices in supportive care and management of prostate cancer patients. The survey was distributed to lead radiotherapy personnel in radiotherapy services across the UK with a 77% response rate (n = 54). RESULTS: Pre-treatment protocols were mandated in the majority of departments. Use of bladder filling (98%) and bowel emptying (66%) were frequently deployed. Bowel preparation varied between use of laxatives (13%) or enemas (41%) to achieve consistency. On-treatment reviews were carried out by a mix of health professionals; most commonly shared between oncologists and radiographers (20%). Radiographers reviewing patients were independent prescribers in 22% of departments. Toxicity grading tools were not used by almost half of departments (47%) either at baseline and/or on-treatment reviews. Written information about follow-up was given to patients towards the end of their radiotherapy; however, fewer departments included the length of hormone duration (13%). CONCLUSION: This survey has demonstrated variations in practice exist across the UK. These variations suggest that important questions about the best methods for treatment accuracy and patient management need to be established through further research.

Post-chemotherapy retroperitoneal lymph node dissection in the management of metastatic testis cancer: the 16-year experience in an Irish setting.

INTRODUCTION: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important tool in the management of advanced germ cell testis cancer, particularly non-seminoma. AIM: 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. METHODOLOGY: 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. RESULTS: 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). CONCLUSION: 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.

International students' experience of a western medical school: a mixed methods study exploring the early years in the context of cultural and social adjustment compared to students from the host country.

BACKGROUND: Few studies have addressed the challenges associated with international students as they adapt to studying medicine in a new host country. Higher level institutions have increasing numbers of international students commencing programmes. This paper explores the experiences of a cohort of students in the early years of medical school in Ireland, where a considerable cohort are from an international background. METHODS: A mixed exploratory sequential study design was carried out with medical students in the preclinical component of a five year undergraduate programme. Data for the qualitative phase was collected through 29 semi-structured interviews using the peer interview method. Thematic analysis from this phase was incorporated to develop an online questionnaire combined with components of the Student Adaptation to College Questionnaire and Student Integration Questionnaire. First year students were anonymously surveyed online. The Mokken Scaling procedure was used to investigate the students' experiences, both positive and negative. RESULTS: Three main themes are identified; social adjustment, social alienation and cultural alienation. The response rate for the survey was 49% (467 Respondents). The Mokken Scaling method identified the following scales (i) Positive experience of student life; (ii) Social alienation, which comprised of negative items about feeling lonely, not fitting in, being homesick and (iii) Cultural alienation, which included the items of being uncomfortable around cultural norms of dress and contact between the sexes. With the threshold set to H = 0.4. Subscales of the positive experiences of student life scale are explored further. CONCLUSIONS: Overall student adjustment to a western third level college was good. Students from regions where cultural distance is greatest reported more difficulties in adjusting. Students from these regions also demonstrate very good adaptation. Some students from the host country and more similar cultural backgrounds were also struggling. Acculturation is more complex than being associated with cultural distance and worthy of further exploration.

Adverse events in healthcare: learning from mistakes.

Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.

The anatomy room: a positive learning experience for nursing students.

BACKGROUND: Management of death and dying is an important aspect of nursing practice. Many nursing students have not been exposed to death prior to their commencement in nurse education and typically do not encounter dying and death until their clinical experience begins. OBJECTIVES: To examine the effects and impact of exposure of nursing students to an anatomy room for anatomy teaching compared with students taught anatomy in a laboratory using plastic anatomical specimens. METHODS: Two groups of first year nursing students were surveyed; one group received tuition in anatomy using plastic specimens and the second group used dissected cadavers. Questionnaires were administered before and immediately after the first teaching experience and again 9 weeks later. RESULTS: Students studying anatomy using cadaveric specimens were more apprehensive of subsequent visits to the anatomy room. However, after 9 weeks there was no significant difference when compared to students using plastic specimens. The students using cadavers felt significantly more stressed and reported significantly more symptoms than those using plastic specimens after their first lesson. There was no significant difference in stress levels and symptom reporting between the groups after 9 weeks. While a large proportion of the students using both cadavers (97%) and plastic specimens (88%) found their learning experiences positive, 43% of the respondents using cadavers stated that as a result of this experience they felt more prepared to deal with death in a hospital and that they were happy to see death in a stress free environment. The responses from the group using plastic specimens were positive as essentially they had found the theory easier to learn. CONCLUSIONS: The results suggest that learning anatomy using cadavers is a beneficial learning experience and could be a valuable way to encounter death for the first time in a protected environment rather than in the clinical setting.

Sex trafficking in Ireland from a health care perspective.

Sex trafficking within Ireland is a hidden phenomenon. In 2010, 78 alleged victims were reported to An Garda Siochina and the recorded levels of human trafficking into Ireland have remained at this level for the last four years. Despite this, no Irish guidelines or referral pathways exist to assist health care professionals. This paper highlights that health care professionals are not aware of this occurrence nor have they been trained to identify victims. Due to a lack of awareness many potential opportunities to detect these victims may be missed. While there is no single set of symptoms or signs that differentiates sex-trafficked victims from other sex workers, an awareness of common physical and psychological health problems associated with sex trafficking by health care professionals may increase victim detection rates. This paper summarises indicators, approach mechanisms, screening questions and a referral guideline relevant to the Irish health care system. This step-by-step guide can be used by health care professionals who encounter such a situation.

Does pain mediate or moderate the relationship between physical activity and depressive symptoms in older people? Findings from The Irish Longitudinal Study on Ageing (TILDA).

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.

Plasma advanced glycation end products (AGEs), receptors for AGEs and their correlation with inflammatory markers in middle school-age children.

AIM: Advanced glycation end products (AGEs) and/or their receptors (RAGE) are significantly positively correlated with adiposity, inflammation, dyslipidemia, and insulin resistance in adults. However, the relationships between AGEs, RAGE, and adiposity-related comorbidites in children have not been well studied. METHODS: In a cross-sectional study of 88 children (age 11-15 years) from the New York area enrolled in the Reduce Obesity and Diabetes (ROAD) study, we examined the correlation of the AGE N(ε)-(carboxymethyl)lysine (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) with adiposity, inflammatory markers [interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α], adiponectin, lipids, insulin sensitivity, and insulin secretory capacity. RESULTS: Pediatric CML levels were ~20% below average adult levels. CML was significantly (p < 0.05) positively correlated with age and insulin sensitivity and negatively with adiposity, dyslipidemia and IL-6. sRAGE correlated positively with esRAGE and negatively with adiposity and IL-6. Both sRAGE and esRAGE correlated negatively with insulin secretory capacity. CONCLUSION: Our findings suggest that unlike adults, CML is negatively associated with adiposity and adiposity-related comorbidity risk in children. As in adults, sRAGE and esRAGE were, to varying degrees, negatively correlated with body fatness and risk factors for adiposity-related comorbidities.

The Distribution of PSA Age-Specific Profiles in Healthy Irish Men between 20 and 70.

Background. Ireland is estimated to have the highest European incidence rate of prostate cancer (Pca) in 2006 which will increase by 275% by 2025. This study aimed to determine PSA cutoff values in different age groups of healthy male patients without Pca. Methods. 660 men in a pilot men's health programme, aged 18-67, had PSA assayed. Men were grouped into 8 age groups at 5-year intervals: 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 64-70. Results. Linear regression demonstrates a PSA velocity of 0.024 ng/ml/year. The 95% confidence interval demonstrates a near flat line of PSA values from age 20 to 50 and rises after. When transformed logarithmically, PSA correlates highly with expected values from the normal distribution (0.98). A fractional polynomial quantile regression model was used to predict median and 95th percentile for PSA as follows: 30-34 (0.73, 1.57), 35-39 (0.71, 1.65), 40-44 (0.73, 1.85), 45-49 (0.78, 2.17), 50-54 (0.88, 2.63), 55-59 (1.01, 3.25), 60-64 (1.20, 4.02), and 64-70 (1.43, 4.96). Conclusions. PSA levels are similar to other racial groups but not as high as US Caucasians until 65 years. These data define the predicted PSA for the Irish population and provide a reference for future screening programmes.

The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity.

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. <37 weeks of gestation) and miscarriage rate (<24 weeks of gestation). RESULTS: Out of 1808 women who underwent LLETZ treatment, a total of 353 women were identified who subsequently had a pregnancy at the CWIUH, with 321 being eligible for inclusion in the study. Of these, 76.3% delivered at term, 9.1% delivered at <37 weeks of gestation and 14.6% miscarried at <24 weeks of gestation. There was a three-fold increase in the risk of PTL if the excision volume exceeded 6 cm(3) (RR = 3.00; 95% CI 1.45-5.92), or when the thickness of the excised tissue was greater than 12 mm (RR = 2.98; 95% CI 1.27-7.01). The time interval between LLETZ and pregnancy did not appear to have an effect on PTL rates. We found no association between the grade of CIN and the risk of PTL. CONCLUSIONS: This study reveals that the thickness and the total volume of the excised transformation zone are associated with an increased risk of PTL. Excisions thicker than 1.2 cm and larger than 6 cm(3) carry a three times greater risk for PTL.

Young adults' preferred options for receiving chlamydia screening test results: a cross-sectional survey of 6085 young adults.

We investigated how young adults aged 18-29 years would like to be notified of chlamydia screening test results, and, when they test positive, their willingness and preferred mechanism for informing their partners. We conducted a cross-sectional survey of 6085 young adults and found that a call to their mobile phone was their preferred way of receiving positive test results (selected by 50%), followed by email. Text messages (short message service [SMS]) and calls to landline phones were unpopular options, selected by between 5 and 10%. Over 75% of respondents stated they would inform their current partner of a positive chlamydia diagnosis, and 50% would inform their previous partners. Most were willing to receive yearly reminders to go for a chlamydia test. Young adults preference for being informed of chlamydia test results by mobile phone call, rather than by email or SMS text, especially if they test positive, suggests they place high value on the security of the communication mechanism. Offering a range of mechanisms for receipt of test results may increase the acceptability and coverage of sexually transmitted infection (STI) control strategies.

Compliance with follow up cytology after discharge from the colposcopy clinic.

Cervical cancer represents the second common cancer in women and is a major public health issue in Ireland and worldwide. Despite appropriate treatment of precancerous lesions, women with dysplasia are at relatively increased risk, and require follow up. We aimed to evaluate the compliance rate with follow up cytology advice given to patients discharged from the colposcopy clinic and to identify predictive factors for poor compliance. This is a retrospective cohort study of patients initially managed in our institution in 2001. Patients were evaluated for adherence with the recommendations received at the time of discharge from the clinic. Of the 116 women that were initially contacted, 100 agreed to participate in the study (86% response rate). Sixty women (60%) were entirely compliant. While older patients (> 40 years) were significantly less likely to show complete compliance (OR: 0.12; 950/ Cl: 0.02-0.58; p = 0.009).

Is simple nephrectomy truly simple? Comparison with the radical alternative.

BACKGROUND: The Oxford English dictionary defines the term "simple" as "easily done" and "uncomplicated". We tested the validity of this terminology in relation to open nephrectomy surgery. METHODS: Retrospective review of 215 patients undergoing open, simple (n = 89) or radical (n = 126) nephrectomy in a single university-affiliated institution between 1998 and 2002. Operative time (OT), estimated blood loss (EBL), operative complications (OC) and length of stay in hospital (LOS) were analysed. Statistical analysis employed Fisher's exact test and Stata Release 8.2. RESULTS: Simple nephrectomy was associated with shorter OT (mean 126 vs. 144 min; p = 0.002), reduced EBL (mean 729 vs. 859 cc; p = 0.472), lower OC (9 vs. 17%; 0.087), and more brief LOS (mean 6 vs. 8 days; p < 0.001). CONCLUSIONS: All parameters suggest favourable outcome for the simple nephrectomy group, supporting the use of this terminology. This implies "simple" nephrectomies are truly easier to perform with less complication than their radical counterpart.

What predicts depression in cardiac patients: sociodemographic factors, disease severity or theoretical vulnerabilities?

Depression is associated with increased cardiovascular risk in acute coronary syndrome (ACS) patients, but some argue that elevated depression is actually a marker of cardiovascular disease severity. Therefore, disease indices should better predict depression than established theoretical causes of depression (interpersonal life events, reinforcing events, cognitive distortions, type D personality). However, little theory-based research has been conducted in this area. In a cross-sectional design, ACS patients (n = 336) completed questionnaires assessing depression and psychosocial vulnerabilities. Nested logistic regression assessed the relative contribution of demographic or vulnerability factors, or disease indices or vulnerabilities to depression. In multivariate analysis, all vulnerabilities were independent significant predictors of depression (scoring above threshold on any scale, 48%). Demographic variables accounted for <1% of the variance of depression status, with vulnerabilities accounting for significantly more (pseudo R² = 0.16, χ²(change) = 150.9, df = 4, p < 0.001). Disease indices accounted for 7% of the variance in depression (pseudo R² = 0.07, χ² = 137.9, p < 0.001). However, adding the vulnerabilities increased the overall variance explained to 22% (pseudo R² = 0.22, χ² = 58.6, df = 4, p < 0.001). Theoretical vulnerabilities predicted depression status better than did either demographic or disease indices. The presence of these proximal causes of depression suggests that depression in ACS patients is not simply a result of cardiovascular disease severity.

Prediction of peripartum hysterectomy and end organ dysfunction in major obstetric haemorrhage.

OBJECTIVES: The aims of this study are to determine the incidence and aetiology of major obstetric haemorrhage (MOH) in our population, to examine the success rates of medical and surgical interventions and to identify risk factors for peripartum hysterectomy and end organ dysfunction (EOD). STUDY DESIGN: This prospective study from 2004 to 2007 was carried out in three Dublin maternity hospitals. Women were identified as having MOH if they received ≥5 units of red cell concentrate (RCC) acutely. Risk factors for hysterectomy or end organ dysfunction were calculated using logistic regression. RESULTS: One hundred and seventeen cases of MOH in 93,291 deliveries were identified (1.25/1000). The predominant cause was uterine atony. Haemostasis was achieved with medical therapy alone in 15% of cases. The hydrostatic balloon and the B-Lynch suture arrested bleeding in 75% and 40% of cases utilised respectively. Hysterectomy was required to arrest bleeding in 24% of women and 16% of women developed end organ dysfunction (11 had both). There was one maternal death. Independent risk factors for hysterectomy included the number of previous caesarean sections (OR 3.28, 95% CI 1.95-5.5), placenta praevia (OR 13.5, 95% CI 7.7-184), placenta accreta (OR 37.7, 95% CI 7.7-184), uterine rupture (OR 7.25, 95% CI 1.25-42) and the number of units of RCC transfused (OR 1.31, 95% CI 1.13-1.5). Independent risk factors for end organ dysfunction (EOD) were placenta accreta (OR 5, 95% CI 1.5-16.5), uterine rupture (OR 13.86, 95% CI 2.32-82), the number of RCC transfused (OR 1.31, 95% CI 1.13-1.5) and the minimum haematocrit recorded (OR 5.53, 95% CI 1.7-18). CONCLUSIONS: MOH is complicated by hysterectomy in 24% and end organ dysfunction in 16% of cases. The risk of peripartum hysterectomy is increased with the number of previous caesarean sections, the aetiology of the bleed, namely placenta praevia/accreta or uterine rupture and the volume of blood transfused. Critically, failure to maintain optimal haematocrit during the acute event was associated with end organ dysfunction.

Epileptic tolerance is associated with enduring neuroprotection and uncoupling of the relationship between CA3 damage, neuropeptide Y rearrangement and spontaneous seizures following intra-amygdala kainic acid-induced status epilepticus in mice.

Brief, non-harmful seizures can activate endogenous protective programmes which render the brain resistant to damage caused by prolonged seizure episodes. Whether protection in epileptic tolerance is long-lasting or influences the subsequent development of epilepsy is uncertain. Presently, we investigated the relationship between hippocampal pathology, neuropeptide Y rearrangement and spontaneous seizures in sham- and seizure-preconditioned mice after status epilepticus induced by intra-amygdala kainate. Seizure-induced neuronal death at 24 h was significantly reduced in the ipsilateral hippocampal CA3 and hilus of tolerance mice compared to sham-preconditioned animals subject to status epilepticus. Damage to the CA3-hilus remained reduced in tolerance mice 21 days post-status. In sham-preconditioned mice subject to status epilepticus correlative statistics showed there was a strong inverse relationship between CA3, but not hilar, neuron counts and the number of spontaneous seizures. A strong positive association was also found between neuropeptide Y score and spontaneous seizure count in these mice. In contrast, there was no significant association between spontaneous seizure count and CA3 neuron loss or neuropeptide Y rearrangement in the tolerance mice. These data show that tolerance-conferred neuroprotection is long-lasting and that tolerance disrupts the normal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model.