Real-Time Electron Solvation Induced by Bursts of Laser-Accelerated Protons in Liquid Water.

Understanding the mechanisms of proton energy deposition in matter and subsequent damage formation is fundamental to radiation science. Here we exploit the picosecond (10^{-12} s) resolution of laser-driven accelerators to track ultrafast solvation dynamics for electrons due to proton radiolysis in liquid water (H_{2}O). Comparing these results with modeling that assumes initial conditions similar to those found in photolysis reveals that solvation time due to protons is extended by >20 ps. Supported by magnetohydrodynamic theory this indicates a highly dynamic phase in the immediate aftermath of the proton interaction that is not accounted for in current models.

Impact of timing of delivery on maternal and neonatal outcomes for women after three previous caesarean deliveries; a secondary analysis of the caesarean section registry.

BACKGROUND: As more women are presenting with three previous caesarean deliveries (CD), providers may suggest early term delivery as a means to avoid the risk of spontaneous labour and associated maternal morbidity. OBJECTIVE: To determine whether early term delivery is associated with lower maternal and neonatal morbidity for women with three previous CD. STUDY DESIGN: Secondary analysis of a prospective registry of CD at 19 US academic centres from 1999 to 2002. POPULATION: Women with three previous CD undergoing scheduled or emergent delivery with live, singleton gestations 37-41+ weeks of gestation were included. Women with non-low transverse incisions, antepartum stillbirth, previous myomectomy, fetal anomalies, more or fewer than three previous CD or attempting trial of labour after caesarean section were excluded. METHODS: Gestational age was categorised by week. We fitted logistic regression models to adjust for clinically relevant or statistically significant confounders. MAIN OUTCOME MEASURES: The primary and secondary outcomes were composites, respectively, of maternal and neonatal morbidity. RESULTS: In all, 821 women met the inclusion criteria; maternal morbidity composite occurred in 9.86% and neonatal morbidity occurred in 10.5%. After adjusting for confounding variables, maternal and neonatal morbidity occurred least frequently at 39 weeks. CONCLUSIONS: In women with three previous CDs, adverse maternal outcomes do not increase with increasing gestational age beyond 37 weeks but early term elective repeat CDs are associated with higher neonatal morbidity. Elective delivery of women with three previous CD at 39 weeks of gestation is safe in the absence of maternal or fetal indications for early term delivery. TWEETABLE ABSTRACT: Delivery of women with three previous caesarean deliveries at 39 weeks, in the absence of maternal or fetal indications for early term delivery, is associated with decreased maternal morbidity.

Inappropriate colonoscopic surveillance of hyperplastic polyps.

Colonoscopic surveillance of hyperplastic polyps alone is controversial and may be inappropriate. The colonoscopy surveillance register at a university teaching hospital was audited to determine the extent of such hyperplastic polyp surveillance. The surveillance endoscopy records were reviewed, those patients with hyperplastic polyps were identified, their clinical records were examined and contact was made with each patient. Of the 483 patients undergoing surveillance for colonic polyps 113 (23%) had hyperplastic polyps alone on last colonoscopy. 104 patients remained after exclusion of those under appropriate surveillance. 87 of the 104 patients (84%) were successfully contacted. 37 patients (8%) were under appropriate colonoscopic surveillance for a significant family history of colorectal carcinoma. 50 (10%) patients with hyperplastic polyps alone and no other clinical indication for colonoscopic surveillance were booked for follow up colonoscopy. This represents not only a budgetary but more importantly a clinical opportunity cost the removal of which could liberate valuable colonoscopy time for more appropriate indications.

Endoscopic ultrasound with fine needle aspiration and biopsy in lung cancer and isolated mediastinal lymphadenopathy.

Endoscopic ultrasound with fine-needle aspiration and biopsy (EUS-FNAB) is well established in diagnosing and staging lung cancer in patients with mediastinal adenopathy. EUS-FNAB is highly sensitive, less invasive and has lower complication rates when compared to surgical staging of mediastinal nodes. In this study we describe our experience of EUS-FNAB in lung cancer and other causes of mediastinal lymphadenopathy. EUS-FNAB was performed for assessment of PET positive mediastinal lymph nodes between January 2007 and March 2009 in AMNCH. The endpoints of our study were sensitivity and specificity of EUS-FNAB, morbidity and length of hospital stay. Thirty four patients underwent EUS-FNAB during the study period for both diagnosis and staging. Thirty patients had positive lymph node invasion and 4 had no evidence of malignant invasion. In these 4 patients negative cytology was confirmed on mediastinoscopy giving EUS-FNAB a sensitivity and specificity of 100%. EUS-FNAB upstaged the disease in 12 patients. EUS-FNAB is a reliable tool for mediastinal staging in lung cancer, significantly reducing the need for surgical staging procedures in patients with suspected mediastinal involvement.

Burnout and stress amongst interns in Irish hospitals: contributing factors and potential solutions.

BACKGROUND: The transition from medical school to internship can be daunting for newly qualified doctors. High rates of stress and burnout have been reported, with negative impacts on patient care and physician wellbeing. AIMS: We surveyed interns in our hospital group to evaluate rates of stress and burnout, as well as identify the causative factors and propose potential solutions to these. METHODS: A hundred and one interns working in four different hospitals over a 2-year period were invited to participate in an anonymous survey. The survey collected basic demographic details and surveyed aspects of mental health using the burnout scale, Maslach Burnout Inventory (MBI) and the stress scale and 12-item General Health Questionnaire (GHQ-12). Interns were also asked to rate a variety of workplace factors on a Likert scale based on the degree of stress caused. Finally, they were surveyed on their awareness of support services available to them. RESULTS: Our results showed that 37% of interns met the criteria for psychological distress, high levels of emotional exhaustion, high depersonalisation and a low sense of personal accomplishment were reported in 55.4, 51.5 and 41.6%, respectively. Inadequate preparation for practice, financial worries, poor role definition and sleep deprivation were reported as significant stressors. Most were unaware of available support services and expressed interest in leaving Ireland after internship. CONCLUSIONS: Burnout and stress are significant problems amongst doctors in Irish hospitals. Ensuring better preparation for clinical practice and awareness of support services is vital to tackle this issue.

Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection.

Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.

Surgical and smoking history in inflammatory bowel disease: a case-control study.

: An inverse relation between appendectomy and ulcerative colitis and smoking and ulcerative colitis has been proposed. Our study examined the frequency of common surgical interventions and of smoking in 500 patients with inflammatory bowel disease. They comprised 177 patients with ulcerative colitis, 134 patients with Crohn's disease, and 189 controls matched for age, sex, and socioeconomic group. Subjects were questioned on all previous surgery and on smoking history. The appendectomy rate among controls was 17.5% (33 of 189), which was significantly greater than that of patients with ulcerative colitis: 8.5% (15 of 177; p < 0.05). However, after using multiple variable logistic regression analysis, this was no longer statistically significant. There was no significant difference in appendectomy rate between patients with Crohn's disease and controls. The three groups had comparable rates of tonsillectomy and cholecystectomy. Of patients with ulcerative colitis, 84.2% were nonsmokers at the time of diagnosis in contrast to 50.4% among the patients with Crohn's disease (p < 0.01). In this case-control study, by using multivariate logistic regression analysis, appendectomy offers no significant protection from developing ulcerative colitis or Crohn's disease. Smoking appears to be deleterious in Crohn's disease, whereas a cessation of smoking precedes the onset of ulcerative colitis in a significant number of cases.

Screening for Helicobacter pylori in young dyspeptic patients referred for investigation--endoscopy for those who test negative.

BACKGROUND: Studies in young dyspeptic patients have suggested that screening strategies based on non-invasive H. pylori testing can reduce endoscopy workload by 25-40%. Such strategies usually propose that only H. pylori-positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease. AIM: To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori-negative dyspeptics. METHODS: Seventy-two consecutive patients under 45 years of age undergoing investigation for 'ulcer-like' dyspepsia had invasive and non-invasive determination of H. pylori status. Individuals found to be H. pylori-positive at endoscopy received 1 week of proton pump inhibitor-based triple therapy. H. pylori-negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically-positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy. RESULTS: According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow-up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically-positive patients would ultimately have required an endoscopy and the other 25 serologically-positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically-negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population. CONCLUSION: A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.

Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice.

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.

CSF concentrations of neurotensin in schizophrenia: an investigation of clinical and biochemical correlates.

Neurotensin (NT), a peptide which colocalizes with dopamine in some midbrain and hypothalamic neurons, has been speculated to play a role in schizophrenic illness and in the action of antipsychotic drugs. Previous work suggested a bimodal distribution of NT in patients with schizophrenia, with a subgroup having low drug-free NT concentrations which normalize with neuroleptic treatment. We studied 15 schizophrenic patients with CSF samples collected both off and on neuroleptic medication, 12 with only drug-free (DF) samples, and 10 controls. There was no significant difference in CSF NT concentrations between patients and controls, or between patients off and on medication. However, 7 patients with DFNT CSF concentrations below the patient mean showed an increase with neuroleptic treatment. Moreover, NT was significantly lower for women. Significant correlations with NT concentrations in CSF were found with deficit symptoms in patients, and with the age of the CSF sample for all subjects. There was no correlation between CSF NT concentrations and patient age, duration of illness, or levels of amine metabolites (MHPG, 5HIAA, HVA).

Increased mast cells in the irritable bowel syndrome.

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.

DNA repair and mutant frequency in schizophrenia.

The in vivo frequency of mutants resulting from mutation at the hprt locus in human T-lymphocytes was determined with a cloning assay. T-lymphocytes were obtained from 14 individuals diagnosed with schizophrenia and 5 controls. No significant difference in mutant frequency was observed between the 2 groups. In addition, DNA-repair capacity was measured with the unscheduled DNA synthesis technique in lymphocytes from 7 individuals diagnosed with schizophrenia and 7 controls. Repair capacity was determined following treatment with MMS, MNNG, and 20 J/m2 ultraviolet light. No significant differences in DNA repair were observed between the patient and control groups in response to any of the 3 DNA-damaging agents. These results argue against differences between normal and schizophrenic individuals with respect to in vivo mutant frequency or their capacity to repair DNA lesions induced by MMS, MNNG, or ultraviolet radiation.

Survey of current practices among members of CAG in the follow-up of patients diagnosed with gastric ulcer.

INTRODUCTION: Guidelines recommend a policy of endoscopic follow-up of all gastric ulcers until healing. Analysis of data from the Alberta Endoscopy Project indicates that fewer than 50% of patients diagnosed with benign gastric ulcer had undergone a repeat procedure. The practice and attitudes of physician members of the Canadian Association of Gastroenterology (CAG) on the follow-up of such patients were assessed. METHODS: A self-administered questionnaire was mailed to members of CAG. Respondents were asked to indicate their practice setting and to estimate the proportion of gastric ulcer patients in whom they perform follow-up endoscopy. They were also asked to indicate factors influencing this choice, including the role of Helicobacter pylori. RESULTS: Fifty-seven per cent of 220 respondents indicated that they perform repeat endoscopy in 95% to 100% of individuals with benign gastric ulcer. The most common reasons influencing this choice were to ensure healing (86.3%) and to confirm the benign nature of the lesion (79.5%). Nonsteroidal anti-inflammatory drug (NSAID) use (83.2%) and patient ill health (62.9%) were the most common reasons for not repeating the endoscopy. Twenty per cent of individuals indicated that H pylori had influenced a change in their practice. DISCUSSION: Physicians vary widely in their follow-up of benign gastric ulcer. Studies on the occurrence of gastric cancer in this setting are not unanimous in their conclusions. Subgroups of patients with NSAID exposure and successfully eradicated H pylori infection may have a lower risk of malignancy. Studies to confirm this are warranted, and modified guidelines may be appropriate.

Validation of serological tests for Helicobacter pylori infection in an Irish population.

BACKGROUND: Serological tests for Helicobacter pylori using laboratory and 'office' formats are commonly used, easy to perform, inexpensive and widely available. Local validation of test performance is required. AIMS: This study examined the performance of a laboratory and 'office' ELISA in a population of Irish dyspeptics presenting for endoscopy. METHODS: Consecutive patients presenting for endoscopy had blood drawn at sedation. Samples were analysed using two ELISA formats; a standard laboratory format and an 'office' ELISA test card. H. pylori infection was diagnosed by analysis of antral and corpus biopsies using the rapid urease test, culture and histology. A combination of two positive invasive tests was considered indicative of infection. RESULTS: The sensitivity and specificity of laboratory ELISA was 82.4% and 85% respectively while the values for the 'office' ELISA were 87.7% and 85.7% respectively. In patients under 45 years sensitivities and specificities of the 'office' test exceeded 90%. The two serological tests agreed in 87.5% of subjects. CONCLUSIONS: Both tests performed satisfactorily. However, indeterminate results impaired the usefulness of the laboratory ELISA particularly when using a new cut-off. The 'office' ELISA performed particularly well in young patients. A simpler test using antigens from locally prevalent strains to optimise accuracy is awaited.

The effects of blood on rapid urease testing for Helicobacter pylori in mucosal biopsies from the gastric antrum.

BACKGROUND: While the eradication of Helicobacter pylori in patients with bleeding peptic ulcer disease (PUD) decreases the rate of ulcer re-bleeding, the sensitivity of the rapid urease test (RUT) for H. pylori diagnosis is lower in this setting. The aim of this study was therefore to determine if exposing a gastric biopsy specimen to blood before its use in the RUT (CLOtest) could account for these findings. METHODS: In patients undergoing endoscopy for the evaluation of dyspepsia gastric mucosal biopsies were obtained for H. pylori diagnosis (RUT, microbiology, and histology). Mucosal biopsies from each patient were also exposed to blood for 15, 30 and 45 minutes before use in the RUT. RESULTS: Using a combination of diagnostic tests (histology, microbiology and routine CLOtest) as the 'gold standard', the sensitivity, specificity, positive predictive value and negative predictive value of the CLOtest remained above 90% despite prior exposure of the gastric biopsy specimen to blood, and these values were not significantly different from the performance characteristics of the CLOtest processed in a routine manner. CONCLUSION: The exposure of gastric mucosal biopsy specimens to blood alone is not the explanation for the reduced sensitivity of the RUT in patients with bleeding peptic ulcers.

Helicobacter pylori resistance rates for levofloxacin, tetracycline and rifabutin among Irish isolates at a reference centre.

INTRODUCTION: Helicobacter pylori eradication rates using conventional triple therapies are falling, making viable second-line and rescue regimens necessary. Levofloxacin, tetracycline and rifabutin are three efficacious antibiotics for rescue therapy. AIM: We aimed to assess the resistance rates for H. pylori against these antibiotics in an Irish cohort. METHODS: Gastric biopsies were collected from 85 patients infected with H. pylori (mean age 46 years) in the Adelaide and Meath Hospital, Dublin in 2008 and 2009. Susceptibility to antibiotics was tested using the Etest. Clinical information was obtained from endoscopy reports and chart review. RESULTS: 50.6 % of patients were females. Mean age was 47 years. Ten had prior attempts at eradication therapy with amoxicillin-clarithromycin-PPI, two had levofloxacin-based second-line therapy. 11.7 % [95 % CI (6.5-20.3 %)] (N = 10) had strains resistant to levofloxacin. There were no strains resistant to rifabutin or tetracycline. Levofloxacin resistance in the under 45 age group was 2.6 % (1/38) compared to 19.1 % (9/47) of above 45 age group (p = 0.02). DISCUSSION: The levofloxacin rates illustrated in this study are relatively low by European standards and in line with other studies from the United Kingdom and Germany, with younger patients having very low levels of resistance. Levofloxacin, tetracycline and rifabutin are all valid options for H. pylori eradication in Irish patients but the importance of compliance cannot be underestimated.

A changing trend in the management of patients with newly diagnosed Crohn's disease.

BACKGROUND: Epidemiologic shift with rising incidence of Crohn's disease (CD) has been reported in recent studies. AIMS: To determine disease behaviour and therapeutic interventions undertaken in newly diagnosed patients with CD. METHODS: Patients diagnosed with CD between January 2006 and June 2008 were included. Disease type, location, degree of involvement and type of therapeutic interventions were recorded. RESULTS: A total of 78 patients were included. Colonic, ileo-colonic, terminal ileal and isolated small bowel disease were present in 37, 27, 9 and 5 patients, respectively. Disease phenotype was inflammatory, stenosing and fistulising in 42, 30 and 6 patients, respectively. Surgery was required in 22 patients, including right hemicolectomy (n = 8), subtotal colectomy (n = 4), segmental colonic resection (n = 2), segmental small bowel resection (n = 2), appendectomy (n = 2) and perianal surgery (n = 4). Fourteen patients underwent surgery at the time of diagnosis. Laparoscopic surgery was performed in 14 patients. CONCLUSIONS: A significant proportion of newly diagnosed patients with CD underwent surgical intervention on their first admission to hospital. This may signify a changing trend in the management approach.

A comparative study of faecal occult blood kits in a colorectal cancer screening program in a cohort of healthy construction workers.

BACKGROUND: The incidence of colorectal cancer (CRC) has been increasing. We evaluated uptake rates and outcomes of faecal immunochemical test (FIT) and Guaiac test (gFOBT) kits as part of a two-step CRC screening. METHODS: A 3-year CRC screening program for a defined population of construction workers was conducted. Those satisfying the inclusion criteria were provided with gFOBT or FIT kits. Individuals testing positive were invited for a colonoscopy. RESULTS: A total of 909 faecal testing kits were distributed. Age range was 53-60 years. Compliance rate was higher for FIT (58.3%) as compared to gFOBT (46.7%) (p = 0.0006). FIT detected adenomatous polyps and CRC in 37.5 and 25%, respectively, whereas; gFOBT detected 23.5 and 18%. Colonoscopies were normal in 53 and 25% tested positive by gFOBT and FIT, respectively (p = 0.016). CONCLUSION: The FIT was more cost-effective when compared with gFOBT with higher return rate, sensitivity and specificity. A comparative study of faecal occult blood kits in a CRC screening program in a healthy cohort of construction workers.