European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

A Survey of Colorectal Cancer Surveillance Practices In Ireland, And Implementation of A Survivorship Care Plan Pilot Programme

Aims The number of colorectal cancer (CRC) survivors in Ireland is rising. We aimed to survey current surveillance practices and pilot the use of survivorship care plans (SCPs) in the clinic. Methods An online survey was issued to medical oncologists (MOs) in designated cancer centres (DCC) and satellite centres. The SCP was piloted in CRC patients and a follow-up questionnaire assessing their views was issued. Results Responses from 8 DCC and satellite centres were obtained (n=13). Routine surveillance is practiced by 77% (n=10) and 69% (n=9) believe that the MO clinic is inappropriate for follow-up. Most think that the SCP is useful and that ANP-led surveillance clinics should be introduced. Of 16 patients who replied to the survey, most felt that the SCP was bene􀂡cial. Sixty-two percent (n=10) were agreeable to GP follow-up using the SCP. Conclusion Surveillance practices in Ireland are heterogeneous. The SCP may be useful for streamlining follow-up practices nationally.

What is the future for General Surgery in Model 3 Hospitals?

BACKGROUND: General Surgery consultant recruitment poses considerable challenges in Model 3 Hospitals in Ireland. AIM: The aim of this paper is to examine General Surgery activity and consultant staffing in order to inform future manpower and service planning. METHODS: General surgical activity in Model 3 Hospitals was examined using the validated 2014 Hospital Inpatient Enquiry (HIPE) dataset. Current consultant staffing was ascertained from hospital personnel departments and all trainees on the National Surgical Training Programme were asked to complete a questionnaire on their career intentions. RESULTS: Model 3 Hospitals accounted for 50% of all General Surgery discharges. In the elective setting, 51.5% of all procedures were endoscopic investigations and in the acute setting only 22% of patients underwent an operation. Most surgical procedures were of low acuity and included excision of minor lesions, appendicectomy, cholecystectomy and hernia repair. Of 76 General Surgeons who work in Model 3 Hospitals 25% were locums and 54% had not undergone formal training in Ireland. A further 22% of these surgeons will retire in the next five years. General Surgical trainees surveyed indicated an unwillingness to take up posts in Model 3 Hospitals, while 83% indicated that a post in a Model 4 Hospital is 'most desirable'. Lack of attractiveness related to issues regarding rotas, lack of ongoing skill enhancement, poor experience in the management of complex surgical conditions, limited research and academic opportunity, isolation from colleagues and poor trainee support. CONCLUSIONS: These data indicated that an impending General Surgery consultant manpower crisis can only be averted in Model 3 Hospitals by either major change in the emphasis of surgical training or a significant reorganisation of surgical services.

Epithelioid Angiomyolipoma - a case report and review of the literature.

Herein we present the case of a 43-year-old female in whom a left renal mass was identified incidentally on imaging performed for staging of a newly diagnosed breast carcinoma. The mass was resected and histologic examination and immunohistochemistry confirmed a diagnosis of epithelioid angiomyolipoma.

Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is common in diabetes and obesity but few have clinically significant liver fibrosis. Improved risk-assessment is needed as the commonly used clinical-risk algorithm, the NAFLD fibrosis score (NFS), is often inconclusive. AIMS: To determine whether circulating fibroblast activation protein (cFAP), which is elevated in cirrhosis, has value in excluding significant fibrosis, particularly combined with NFS. METHODS: cFAP was measured in 106 with type 2 diabetes who had transient elastography (Cohort 1) and 146 with morbid obesity who had liver biopsy (Cohort 2). RESULTS: In Cohort 1, cFAP (per SD) independently associated with median liver stiffness (LSM) ≥ 10.3 kPa with OR of 2.0 (95% CI 1.2-3.4), p=0.006. There was 0.12 OR (95% CI 0.03-0.61) of LSM ≥ 10.3 kPa for those in the lowest compared with the highest FAP tertile (p=0.010). FAP levels below 730 pmol AMC/min/mL had 95% NPV for LSM ≥ 10.3 kPa and reclassified 41% of 64 subjects from NFS 'indeterminate-risk' to 'low-risk'. In Cohort 2, cFAP (per SD), associated with 1.7 fold (95% CI 1.1-2.8) increased odds of significant fibrosis (F ≥ 2), p=0.021, and low cFAP reclassified 49% of 73 subjects from 'indeterminate-risk' to 'low-risk'. CONCLUSIONS: Lower cFAP, when combined with NFS, may have clinical utility in excluding significant fibrosis in diabetes and obesity.

Targeted resequencing of the microRNAome and 3'UTRome reveals functional germline DNA variants with altered prevalence in epithelial ovarian cancer.

Ovarian cancer is a major cause of cancer deaths, yet there have been few known genetic risk factors identified, the best known of which are disruptions in protein coding sequences (BRCA1 and 2). Recent findings indicate that there are powerful genetic markers of cancer risk outside of these regions, in the noncoding mRNA control regions. To identify additional cancer-associated, functional non-protein-coding sequence germline variants associated with ovarian cancer risk, we captured DNA regions corresponding to all validated human microRNAs and the 3' untranslated regions (UTRs) of ~6000 cancer-associated genes from 31 ovarian cancer patients. Multiple single-nucleotide polymorphisms in the 3'UTR of the vascular endothelial growth factor receptor/FLT1, E2F2 and PCM1 oncogenes were highly enriched in ovarian cancer patients compared with the 1000 Genome Project. Sequenom validation in a case-control study (267 cases and 89 controls) confirmed a novel variant in the PCM1 3'UTR is significantly associated with ovarian cancer (P=0.0086). This work identifies a potential new ovarian cancer locus and further confirms that cancer resequencing efforts should not ignore the study of noncoding regions of cancer patients.

The surgical safety checklist survey: a national perspective on patient safety.

BACKGROUND: In 2008, the World Health Organisation (WHO) recommended practices to ensure the safety of patients worldwide. This led to the development of the Surgical Safety Checklist (SSC). Ireland has endorsed the SSC ( www.hiqa.ie/press-release/2008-06-17-health-information-and-quality-authority-launches-world-health-organization , 10). OBJECTIVES: We aimed to determine (i) whether SSC is being implemented, (ii) whether it promotes a safer surgical environment and (iii) identify problems associated with its introduction and on-going implementation. METHODS: All hospitals in Ireland with operating departments (n = 61) were invited to participate in an online survey. RESULTS: The response rate was 67 %. The WHO SSC or modified version is in place in 78 % (mean time: 20 months) of operating departments that responded. Partaking in Time Out as a team was reported as occurring in 57 % of cases. Greater than 60 % of respondents reported that the SSC was difficult to introduce and implement and that its introduction was time consuming. Further training in using the SSC was reported as desirable by 84 % of respondents. The introduction of the SSC was reported to be associated with an improvement in team communication (72 %), a positive change in team behaviour (63 %), an increase in the consistency of patient care (82 %) and a positive culture of safety in theatre (81 %). CONCLUSION: The SSC has not been implemented throughout all operating departments in Ireland. Where it has been introduced there has been a perceived positive change in safety culture. However, overall greater education, endorsement, teamwork, and communication will be required to optimise the potential benefits associated with this safety instrument. In order to properly determine the benefit of the SSC following its implementation, a formal audit of morbidity and mortality is required.

Not so different after all? Comparing patients attending general practice-based locally enhanced services for sexual health with patients attending genitourinary medicine.

We did a cross-sectional survey of patients attending genitourinary (GU) medicine clinics (n = 933) and general practice-based Locally Enhanced Services for Sexual Health (GP-LESSH, n = 111) in Cornwall, England, in 2009/2010, to compare patients' characteristics and experiences. Patients completed a pen-and-paper questionnaire that was then linked to an extract of their clinical data. GP-LESSH patients took longer both to seek and to receive care: medians of nine and seven days, respectively, versus GU medicine patients: medians of seven and one day, respectively. GP-LESSH patients were less likely than GU medicine patients to report symptoms (19.6% versus 30.6%) and sexual risk behaviours (33.3% versus 44.7% reported new partners) since recognizing needing to seek care; 5.0% versus 10.2% were men who have sex with men). However, they were equally likely to have sexually transmitted infections (STIs) diagnosed (23.3% versus 24.8%). As GP-LESSH may operate infrequently, local services must work collaboratively to ensure that those seeking care for suspected STIs receive it promptly. Failing to do so facilitates avoidable STI transmission.

Quality of rectal cancer surgery and its relationship to surgeon and hospital caseload: a population-based study.

AIM: A population-based audit of all rectal cancers diagnosed in Ireland in 2007 has shown an inconsistent relationship between surgeon and hospital caseload and a range of quality measures. Better outcome for rectal cancer has been associated with increasing surgeon and hospital caseload, but there is less evidence of how this may relate to quality of care. Our aim was to examine how measures of quality in rectal cancer surgery related to surgeon and hospital workload and to outcome. METHOD: All colorectal surgeons in Ireland participated in an audit of rectal cancer based on an evidence-based instrument. Data were extracted from medical records by trained coders. Generalized linear mixed models were used to determine the relationship between surgeon or hospital caseload and measures of quality of care. RESULTS: Five hundred and eighty-one (95%) of the 614 rectal cancers diagnosed in Ireland in 2007 were audited; 49 hospitals and 86 surgeons participated. Ten (28%) hospitals treated fewer than five cases and seven fewer than three. A positive relationship between caseload and quality was seen for a few measures, more frequently for hospital than surgeon caseload. The relationship between caseload and quality of care was inconsistent, suggesting these measures do not represent a single dimension of quality. One-year survival was negatively associated with hospital caseload. There was no statistically significant relationship between survival and measures of quality of care. DISCUSSION: Quality of care was inconsistently influenced by surgeon and hospital caseload. Caseload may affect only one aspect of surgical management, such as the quality of preoperative workup, and is not necessarily related to the quality of other hospital care. Simple measures of outcome, such as survival, cannot represent the complexity of this relationship.

Laparoscopic right hemicolectomy for intestinal intussuception.

INTRODUCTION: Adult intussusception is rare and usually associated with carcinoma in 50% of the cases. These have traditionally been managed using an open technique. We herein describe a laparoscopic extended right hemicolectomy in a 62-year-old lady with an intussuception secondary to a transverse colonic tumor. METHODS: The patient presented with 6 weeks of crampy, colicky, abdominal pain. Her CT scan reported intussuception of the proximal large bowel. She underwent an extended laparoscopic right hemicolectomy with primary anastomosis. RESULTS: Her post-operative recovery was uneventful and the histology reported a large bowel adenocarcinoma (pT4, N0, M0) with none out of 25 nodes involved. CONCLUSION: When operative intervention is required, intussuception may be managed using a minimally invasive technique. However, large bowel intussuception in adults may have a malignant cause thus laparoscopic resection should only be performed by surgeons experienced in laparoscopic resections for colorectal malignancies as oncological safety must be the primary concern. This laparoscopic approach facilitates rapid recovery and earlier time to adjuvant therapy if required.

A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer.

Germline variants in the 3' untranslated region (3'UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS variant, is associated with both cancer risk and altered tumor biology. Here, we test the hypothesis that the KRAS variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS variant-positive EOC patients. As this variant seems to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival. EOC patients with complete clinical data were genotyped for the KRAS variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125) and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were used to confirm altered sensitivity to chemotherapy associated with the KRAS variant. Finally, the KRAS variant was directly targeted through small-interfering RNA/miRNA oligonucleotides in cell lines and survival was measured. Postmenopausal EOC patients with the KRAS variant were significantly more likely to die of ovarian cancer by multivariate analysis (hazard ratio=1.67, 95% confidence interval: 1.09-2.57, P=0.019, n=279). Perhaps explaining this finding, EOC patients with the KRAS variant were significantly more likely to be platinum resistant (odds ratio=3.18, confidence interval: 1.31-7.72, P=0.0106, n=291). In addition, direct targeting of the KRAS variant led to a significant reduction in EOC cell growth and survival in vitro. These findings confirm the importance of the KRAS variant in EOC, and indicate that the KRAS variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this study supports the hypothesis that these tumors have continued dependence on such 3'UTR lesions, and that direct targeting may be a viable future treatment approach.

The management of rectal cancer in Ireland in 2007--room for improvement?

INTRODUCTION: Effective management of rectal cancer relies on accurate pre-operative assessment, surgical technical excellence and integrated neoadjuvant and adjuvant chemo and/or radiotherapy. The aim of this study was to examine the management of rectal cancer in Ireland. METHODS: This was a retrospective chart review. All cases of rectal cancer (15 cm or less from the anal verge) diagnosed in Ireland in the year 2007 were included in the audit. RESULTS: In total data for 585 patients were included, under the care of 87 consultant surgeons operating in 48 hospitals. Only data recorded in medical charts were included. Pre-operative investigations were less utilised than recommended by current guidelines and consequently many cancers were inadequately staged. In total 52.5% of cases were discussed at a multi-disciplinary meeting. Overall, 88% of the patients had surgery, and the 30-day mortality rate was 1.7%. The quality of post-operative pathology reporting was variable, with adequacy of total mesorectal excision status unclear or unknown in 74% of cases. Cases were managed in a large number of centres, and in lower volume centres (<5 cases per annum) patients appeared to be less adequately investigated. CONCLUSION: This study gives a snapshot of recent practice in the management of rectal cancer in Ireland but is of necessity limited as the audit was retrospective and long term outcomes have not been assessed. In 2007 rectal cancer was managed in a large number of centres and best practice was frequently not adhered to. The impending centralisation of cancer services is likely to impact on the management of rectal cancer in Ireland.

Patients' attitudes towards increasing the offer of HIV testing in primary and secondary care.

The UK National Guidelines on HIV testing (2008) recommend routinely offering an HIV test to patients in certain clinical settings. We wished to investigate the acceptability of implementing these guidelines in a population with a low HIV prevalence. Patients accessing primary and secondary care were asked to circle one of the five responses to a series of statements regarding HIV testing. Of the 616 respondents, 579 (94%) stated they would be willing to be tested if presenting with a condition known to be associated with HIV. Four hundred and forty out of 616 (71%) stated they would be willing to be tested as part of their routine care, while 445/616 (72%) stated they would be willing to have the result in their main medical notes. Although the patients' responses were largely receptive to increased testing, we encountered notable negative attitudes to the project from professional and administrative staff. Resistance to increased HIV testing may be related to health-care workers rather than patients.

The RAPID protocol enhances patient recovery after both laparoscopic and open colorectal resections.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs can accelerate recovery and shorten the hospital stay after colorectal resections. The RAPID (remove, ambulate, postoperative analgesia, introduce diet) protocol is a simplified ERAS program that consists of a simplified, user-friendly single-page pro forma schedule. This study aimed to evaluate the impact of the RAPID protocol on patients undergoing both laparoscopic and open colorectal resections in two specialized colorectal units. METHODS: A prospective, two-center study assessed 117 age-matched patients undergoing open or laparoscopic colorectal resection to compare the postoperative course for patients using the RAPID protocol with those treated in a traditional manner. RESULTS: Of the 117 patients studied, 70 underwent laparoscopic resection (55 with the RAPID protocol) and 47 underwent open resection (25 with the RAPID protocol). Patients undergoing laparoscopic resections with the RAPID protocol had a significantly shorter hospital stay (p = 0.01) and tolerance of a full diet (p = 0.002). Similarly, patients undergoing open resections with the RAPID protocol also have a significantly shorter hospital stay (p = 0.04). CONCLUSION: The RAPID protocol is a user-friendly, easy, and effective tool that facilitates earlier tolerance of diet and discharge from the hospital for patients undergoing laparoscopic or open colorectal resections.

Do users of the intrauterine system (Mirena) have different genital symptoms and vaginal flora than users of the intrauterine contraceptive device?

The copper intrauterine contraceptive device (IUCD) is strongly associated with bacterial vaginosis (BV). Hormonal influences may play a role in the control of vaginal flora. It is unclear whether use of the progesterone-incorporated intrauterine system (IUS; Mirena) is associated with abnormal vaginal flora or genital symptoms. One hundred and seventy-two women were assessed for symptoms and abnormal vaginal flora prior to and at intervals after insertion of either a copper IUCD or an IUS. Women were significantly more likely to have developed an abnormal vaginal discharge 4-6 weeks after insertion of an IUCD compared with an IUS (27% cf. 14%, P = 0.04), although this trend was not significant six months postinsertion. More women with an IUCD developed BV compared with an IUS at 4-6 weeks and six months. However, there were insufficient numbers of women with BV to demonstrate any significant difference between the vaginal flora of the two groups.

Laparoscopic pelvic sling placement facilitates optimum therapeutic radiotherapy delivery in the management of pelvic malignancy.

BACKGROUND: Radiotherapy has a significant role in the management of pelvic malignancies. However, the small intestine represents the main dose limiting organ. Invasive and non-invasive mechanical methods have been described to displace bowel out of the radiation field. We herein report a case series of laparoscopic placement of an absorbable pelvic sling in patients requiring pelvic radiotherapy. METHODS: Six patients were referred to our minimally invasive unit. Four patients required radical radiotherapy for localised prostate cancer, one was scheduled for salvage localised radiotherapy for post-prostatectomy PSA progression and one patient required adjuvant radiotherapy post-cystoprostatectomy for bladder carcinoma. All patients had excessive small intestine within the radiation fields despite the use of non-invasive displacement methods. RESULTS: All patients underwent laparoscopic mesh placement, allowing for an elevation of small bowel from the pelvis. The presence of an ileal conduit or previous surgery did not prevent mesh placement. Post-operative planning radiotherapy CT scans confirmed displacement of the small intestine allowing all patients to receive safely the planned radiotherapy in terms of both volume and radiation schedule. CONCLUSION: Laparoscopic mesh placement represents a safe and efficient procedure in patients requiring high-dose pelvic radiation, presenting with unacceptable small intestine volume in the radiation field. This procedure is also feasible in those that have undergone previous major abdominal surgery.

The limits of health-care seeking behaviour: how long will patients travel for STI care? Evidence from England's 'Patient Access and the Transmission of Sexually Transmitted Infections' ('PATSI') study.

SUMMARY: The objective of this study was to identify factors associated with (i) longer patient travel time to genitourinary (GU) medicine clinics and (ii) not attending the nearest clinic. Questionnaires were completed by 4600 new attendees from seven sociodemographically and geographically different GU clinics across England between October 2004 and March 2005. These data were then linked to the routine clinic database. Median travel time was 25 minutes and varied significantly by clinic (P < 0.001) but not by gender (P = 0.96). Of all the respondents, 10% spent at least one hour getting to a GU clinic and this was significantly more likely in patients with less education, those who travelled by public transport and those who did not attend their closest clinic. Longer travel times were not associated with delays in seeking care. Patients reporting a previous sexually transmitted infection (STI) diagnosis were more likely not to go to their nearest GU clinic (P = 0.0006), as were those who used/tried to use other health-care providers prior to attending the clinic (P = 0.007). To facilitate access to STI care, comprehensive local services need to be provided to avoid long journey times, especially for those who have to rely on public transport to get to clinic.

Laparoscopic colonic resection in inflammatory bowel disease: minimal surgery, minimal access and minimal hospital stay.

OBJECTIVE: Laparoscopic surgery for inflammatory bowel disease (IBD) is technically demanding but can offer improved short-term outcomes. The introduction of minimally invasive surgery (MIS) as the default operative approach for IBD, however, may have inherent learning curve-associated disadvantages. We hypothesise that the establishment of MIS as the standard operative approach does not increase patient morbidity as assessed in the initial period of its introduction into a specialised unit, and that it confers earlier postoperative gastrointestinal recovery and reduced hospitalisation compared with conventional open resection. METHOD: A case-control study was undertaken on laparoscopic resection (LR) vs open colon resection (OR) for IBD. The LR group was collated prospectively and compared with a pathologically matched historical control set. Outcomes measured included: postoperative length of stay, time to normal bowel function and postoperative morbidity. Statistical analysis was performed using spss. RESULTS: Twenty-eight patients were investigated (14 LR, 14 OR). The two groups were matched for type of operation, type of disease and age. There were no conversions in the LR group. Morbidity and readmissions did not differ significantly between the groups. Those undergoing laparoscopic resection had a quicker return to diet (median 2 vs 4 days; P = 0.000002), time to first bowel motion (2 vs 4 days; P = 0.019) and shorter postoperative length of stay (5.5 vs 12.5; P = 0.0067). CONCLUSION: These findings support the routine use of MIS for the elective surgical management of IBD in our department. Patients undergoing laparoscopic colectomies for IBD can expect faster return of gastrointestinal function and shorter hospitalisation.

Gossypiboma: a case report and review of the literature.

INTRODUCTION: Post-operative complications in surgery may frequently be unavoidable. However, some complications result from human error, both in the intra-operative and post-operative period. One such complication, which is frequently underreported, is the retained swab, or gossypiboma. CASE REPORT: We report a case from our hospital of a patient who presented with unexplained pyrexia, 4 years post-gynaecological surgery in another institution. A 67-year-old woman from overseas presented to our emergency department with a 2-day-history of pyrexia, collapse and confusion. Following a CT guided biopsy, which was inconclusive, she was scheduled for retroperitoneal biopsy. In theatre, a retained swab was discovered. CONCLUSION: Prevention of gossypiboma is far better than cure. Strict adherence to swab counts, and the avoidance of change of staff during procedures is important in decreasing the incidence. Perhaps, with the increasing use of minimally invasive procedures, the incidence of gossypiboma will fall dramatically.