Changes in volume, clinical practice and outcome after reorganisation of oesophago-gastric cancer care in England: A longitudinal observational study.

AIM: The centralisation of oesophago-gastric (O-G) cancer services in England was recommended in 2001, partly because of evidence for a volume-outcome effect for patients having surgery. This study investigated the changes in surgical services for O-G cancer and postoperative mortality since centralisation. METHODS: Patients with O-G cancer who had an oesophageal or gastric resection between April 2003 and March 2014 were identified in the national Hospital Episodes Statistics database. We derived information on the number of NHS trusts performing surgery, their surgical volume, and the number of consultants operating. Postoperative mortality was measured at 30 days, 90 days and 1 year. Logistic regression was used to examine how surgical outcomes were related to patient characteristics and organisational variables. RESULTS: During this period, 29 205 patients underwent an oesophagectomy or gastrectomy. The number of NHS trusts performing surgery decreased from 113 in 2003-04 to 43 in 2013-14, and the median annual surgical volume in NHS trusts rose from 21 to 55 patients. The annual 30 day, 90 day and 1 year mortality decreased from 7.4%, 11.3% and 29.7% in 2003-04 to 2.5%, 4.6% and 19.8% in 2013-14, respectively. There was no evidence that high-risk patients were not undergoing surgery. Changes in NHS trust volume explained only a small proportion of the observed fall in mortality. CONCLUSION: Centralisation of surgical services for O-G cancer in England has resulted in lower postoperative mortality. This cannot be explained by increased volume alone.

Population-based cohort study of the management and survival of patients with early-stage oesophageal adenocarcinoma in England.

BACKGROUND: Until recently, oesophagectomy was the treatment of choice for early oesophageal cancer. Endoscopic treatment has been introduced relatively recently. This observational national database study aimed to describe how endoscopic therapy has been introduced in England and to examine the safety of this approach. METHODS: A population-based cohort study was undertaken of patients diagnosed with oesophageal adenocarcinoma between October 2007 and June 2009 using three linked national databases. Patients with early-stage disease (T1 tumours with no evidence of spread) were identified, along with the primary treatment modality where treatment intent was curative. Short-term outcomes after treatment and 5-year survival were evaluated. RESULTS: Of 5192 patients diagnosed with oesophageal adenocarcinoma, 306 (5·9 per cent) were considered to have early-stage disease before any treatment, of whom 239 (79·9 per cent of 299 patients with data on treatment intent) were managed with curative intent. Of 175 patients who had an oesophagectomy, 114 (65·1 (95 per cent c.i. 57·6 to 72·7) per cent) survived for 5 years. Among these, 47 (30·3 per cent of 155 patients with tissue results available) had their disease upstaged after pathological staging; this occurred more often in patients who did not have staging endoscopic ultrasonography before surgery. Of 41 patients who had an endoscopic resection, 27 (66 (95 per cent c.i. 49 to 80) per cent) survived for 5 years. Repeat endoscopic therapy was required by 23 (56 per cent) of these 41 patients. CONCLUSION: Between 2007 and 2009, oesophagectomy remained the initial treatment of choice (73·2 per cent) among patients with early-stage oesophageal cancer treated with curative intent; one in five patients were managed endoscopically, and this treatment was more common in elderly patients. Although the groups had different patient characteristics, 5-year survival rates were similar.

National survey on endoscopy training in the UK.

INTRODUCTION: Gastrointestinal (GI) endoscopy is an important skill for both gastroenterologists and general surgeons but concerns have been raised about the provision and delivery of training. This survey aimed to evaluate and compare the delivery of endoscopy training to gastroenterology and surgical trainees in the UK. METHODS: A nationwide electronic survey was carried out of UK gastroenterology and general surgery trainees. RESULTS: There were 216 responses (33% gastroenterologists, 67% surgeons). Gastroenterology trainees attended more non-training endoscopy lists (mean: 3.0 vs 1.2) and training lists than surgical trainees (mean: 0.9 vs 0.5). A significantly higher proportion of gastroenterologists had already achieved accreditation in gastroscopy (60.8% vs 28.9%), colonoscopy (66.7% vs 1.4%) and flexible sigmoidoscopy (33.3% vs 3.0%). More gastroenterology trainees aspired to achieve accreditation in gastroscopy (97.2% vs 79.2%), flexible sigmoidoscopy (91.7% vs 70.1%) and colonoscopy (88.8% vs 55.5%) by completion of training. By completion of training, surgeons were less likely than gastroenterologists to have completed the required number of procedures to gain accreditation in gastroscopy (60.3% vs 91.3%), flexible sigmoidoscopy (64.6% vs 68.6%) and colonoscopy (60.3% vs 70.3%). CONCLUSIONS: This survey highlights marked disparities between surgical and gastroenterology trainees in both aiming for and achieving accreditation in endoscopy. Without changes to the delivery and provision of training as well as clarification of the role of endoscopy training in a surgical training programme, future surgeons will not be able to perform essential endoscopic assessment of patients as part of their management algorithm.

Preliminary analysis of demographics and learning attributes of graduate entry medical students.

INTRODUCTION: Students entering university are empowered to move towards self-directed professional learning and beyond didactic tuition. Graduate entry medical (GEM) students have prior experience of this transition from pedagogical to androgogical learning. We aimed to assess the demographics and learning attributes of GEM students. METHODS: Ethical exemption was awarded. The short version of the approaches and study skills inventory for students and the learning style questionnaire were distributed to GEM students during semester 1, 2008. RESULTS: Response rate was 84% (n = 32). Fifty percent of responders had graduated in 2008 (22%) or 2007 (28%). Seventy-five percent had a background in basic science (56%) or an allied health profession (19%). The predominant learning approach is a combination of deep and strategic. The predominant learning style is reflective. CONCLUSIONS: Our preliminary analysis reveals GEM students to exhibit a mature approach to learning and the requisite learning style to achieve academic and clinical success.

Exploring opportunities for collaboration between the corporate sector and the dental education community.

The ultimate purpose of both dental industry and dental education is to improve the oral health of the public. This report provides background information on the different roles and objectives of the dental industry and dental education communities, the different operating environment of each sector and also areas of common interest where collaboration will be of mutual benefit. The report addresses five areas for potential collaboration between the dental industry and the dental education communities: 1. Contribution to joint activities. 2. Effectiveness and efficiency. 3. Workforce needs. 4. Middle- and low-income countries. 5. The future of International Federation of Dental Educators and Associations (IFDEA). The traditional areas of support and their limitations that have been provided by industry are outlined in the report and some new approaches for collaboration are considered. Industry-based research has been an important factor in developing new products and technologies and in promoting oral health. However there is a need to facilitate the introduction of these developments at an early stage in the education process. Industry has to operate in an efficient manner to remain competitive and maximise its returns and therefore survive. The academic sector operates in a different environment and under different governance structures; although some trends are noted towards adoption of greater efficiency and financial accountability similar to industry. Opportunities to jointly develop best business practices should be explored. Industry has responded well to the oral health needs of the public through the development of new products and technologies. The education community needs to respond in a similar way by examining different healthcare delivery models worldwide and developing programmes to train members of the dental team to cater for future needs and demands of communities in different regions of the world. The reputation of industry-based scientists and clinicians is high, and their role in contributing to the dental education process in practical ways needs to be explored and further developed. Closer relationships between industry scientists and faculty and students could assist industrys need and desire to develop new technologies for the broader dental care system. The corporate sector can play a key role in the future success of IFDEA by providing support and expertise in developing areas such as regional leadership institutes, a Global Faculty and Network and in collaborating in developing continuing education programmes as well as involvement in its governance. Thirteen recommendations are made in the report. These are considered to be important initial steps in developing the already strong relationship between the education and corporate sectors. Partnership and collaborating more effectively along the lines suggested should, almost certainly, generate mutually beneficial outcomes, whilst serving over the long term to elevate the publics oral health status on a global basis.

Pneumocystis carinii pneumonia in a patient on etanercept for psoriatic arthritis.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a rare form of pneumonia associated with immune-suppression. It is common in patients with AIDS and with a CD4 count of less than 200 cells/mm(3). We report a case of PCP secondary to immune-suppression in a 41-year-old man with psoriatic arthritis being treated with the immune-modulatory agent etanercept. METHODS: Diagnosis of PCP was made histologically using tissue obtained via transbronchial biopsy. RESULTS: There was a good response to standard treatment with high-dose co-trimoxazole. CONCLUSION: This report highlights a recognised but previously unreported complication of etanercept.

A multimedia approach to raising awareness of information and communications technology amongst healthcare professionals.

This study is concerned with the application of advanced multimedia technology to the development of a programme aimed at raising awareness of information and communications technology (ICT) amongst health professionals in Ireland. The programme is delivered in the form of a symposium supplemented by a multimedia CD and associated web site. It examines how ICT can be used effectively in healthcare across all sectors - primary, secondary and tertiary - with a strong emphasis on supporting shared care. The aim is to empower users to make informed technological choices and to actively participate in the exploitation of ICT in the health sector. The programme was successfully completed and delivered to over 2300 health professionals across Ireland and follow-up activities include the active encouragement of leaders and champions within the sector. This will be supported by interactive web-based education and training material focused on specialised topics of particular interest within the broader context of continuing medical education (CME).

Institutional review boards: changing with the times?

Institutional Review Boards (IRBs) are responsible for safeguarding the rights and welfare of human research subjects. This article describes the changes in the conduct of research and the increasing pressure to conduct more research. Some institutions have not ensured that their IRBs have kept pace with the changing complexity of the research scene. The article discusses the need for a system to protect human subjects that is just as sophisticated as the research enterprise itself. This is increasingly important to justify the public's trust in the research system.

An IT awareness programme for the health sector in Ireland.

This paper describes an Awareness Programme delivered throughout Ireland which aims to increase the level of understanding of healthcare professionals as to the benefits of Information and Communications Technology (ICT) and of emerging trends in Health Informatics in Europe. The programme examines the use of ICT across the whole health sector--primary, secondary and tertiary. It has been delivered at over 30 centres to more than 1500 health professionals.

Historical perspective: Nuremberg, Tuskegee, and the radiation experiments.

AIDS: The National Research Act was passed as a result of the Tuskegee Study, a research study investigating syphilis in black males who received no treatment despite the discovery of penicillin. The Act requires the publication of regulations for the protection of human subjects, as well as requirements for informed consent and review of research by institutional research boards. The 1975 Declaration of Helsinki was also revised. President Clinton, spurned on by reports of humans unknowingly being injected with plutonium for research purposes, created the Advisory Committee on Human Radiation Experiments. The Committee's report culminated in the creation of the National Bioethics Advisory Commission to act as a national deliberative body to advise on the ethical issues faced by the research community today. Despite codes, regulations, and policies, the ultimate protection of research subjects and the future of the research enterprise itself rests with individual investigators and their sense of ethical behavior in fulfilling their obligations to their research subjects.^ieng

Phase I and pharmacokinetic study of taxotere (RP 56976) administered as a 24-hour infusion.

N-Debenzoyl-N-tert-butoxycarbonyl-10-deacytyl taxol (Taxotere, RP 56976) is a semisynthetic analogue of taxol, prepared from a noncytotoxic precursor extracted from the needles of the European yew tree (Taxus baccata L.). It has a broad spectrum of antitumor activity against a variety of transplantable tumors in mice. In vitro cytotoxicity assays suggest that it is 2-5-fold more potent than taxol. In this phase I study Taxotere was administered by 24 h i.v. infusion at 3-week intervals. Thirty patients with solid tumors refractory to conventional therapy were treated; 70 courses of Taxotere were administered at doses ranging from 10 to 90 mg/m2. Grade 4 neutropenia and grade 3 mucositis were dose limiting but reversible at 90 mg/m2. The pattern and grade of toxicity at this dose were similar in 3 heavily pretreated patients compared with 7 patients who had received a maximum of one previous chemotherapy regimen. Alopecia occurred at 55 mg/m2 and above. Other mild toxicities included phlebitis, diarrhea, emesis, and sensory peripheral neuropathy, but these were neither dose-limiting nor clearly dose-related. One patient treated at 70 mg/m2 had an anaphylactoid reaction following the second dose of Taxotere. No cardiovascular toxicity was observed. No partial or complete responses were documented. Plasma concentrations of Taxotere were determined by high-performance liquid chromatography, and end-of-fusion levels at the maximum tolerated dose exceeded drug concentrations which are cytotoxic in vitro. The maximum tolerated dose for Taxotere administered as a 24-h infusion is 90 mg/m2.

Phase I and pharmacokinetic study of rhizoxin.

Rhizoxin is a tubulin-binding cytotoxic compound, isolated from the fungus Rhizopus chinensis, with significant antineoplastic activity in several murine and human tumor models. In this Phase I study, the drug was administered by i.v. bolus injection at 3-wk intervals. Twenty-four patients with refractory solid tumors were treated; 60 courses of rhizoxin were given, at doses ranging from 0.8 to 2.6 mg/m2. Grade 3 mucositis, Grade 4 leukopenia, and Grade 3 diarrhea were dose limiting but reversible at 2.6 mg/m2, the maximum tolerated dose for both previously untreated and heavily pretreated patients. Alopecia and moderate discomfort at the injection site occurred at all doses. Other sequelae, including peripheral neuropathy, phlebitis, and nausea and vomiting, were sporadic and mild. Two heavily pretreated patients with recurrent breast cancer had minor responses to rhizoxin, one at 1.6 mg/m2 and the other at 2.6 mg/m2. Plasma concentrations of rhizoxin were measured by high-performance liquid chromatography. The drug was not detectable (less than 5 ng/ml) at doses of 0.8 mg/m2 and 1.6 mg/m2 and was not measurable 10 min after injection at 2.0 mg/m2. At 2.6 mg/m2, there was considerable intersubject variation in the plasma concentration-time profiles; the area under the curve ranged from 0.29 to 0.96 microgram/ml.min. Rhizoxin has shown some clinical activity in this Phase I study, and a dose of 2.0 mg/m2 is recommended for Phase II studies using this schedule.

Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms.

Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). "Significant" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring.

Obstructive sleep apnea following topical oropharyngeal anesthesia in loud snorers.

Previous studies support the presence of an upper airway reflex mechanism that contributes to the maintenance of upper airway patency during sleep. We investigated the possibility that interference with this reflex mechanism contributes to the development of obstructive sleep apnea. Eight otherwise asymptomatic snorers (seven male and one female), age 39 +/- 5.3 yr (mean +/- SEM), underwent overnight sleep studies on three successive nights. An acclimatization night was followed by two study nights randomly assigned to control (C) and oropharyngeal anesthesia (OPA). On the OPA night topical anesthesia was induced using 10% lidocaine spray and 0.25% bupivacaine gargle. A saline placebo was used on night C. All subjects slept well on both study nights (mean sleep duration was 6.2 h on both study nights), and sleep stage distribution was similar on both nights. Obstructive apneas and hypopneas (OAH) rose from 114 +/- 43 during C to 170 +/- 49 during OPA (p less than 0.02). Central apneas and hypopneas (CAH) were unchanged between the two nights (8 +/- 4.9 versus 7 +/- 3). The duration of OAH was similar on both study nights (20 +/- 1.9 s during C versus 20 +/- 1.5 s during OPA). The frequency of movement arousals terminating OAH tended to be higher during OPA (7 +/- 2.9/h) than during C (3 +/- 0.7); P = NS. The frequency of oxyhemoglobin desaturations was also higher during OPA (5 +/- 2.1/h) than during C (3 +/- 1.4), p less than 0.07.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study.

Recombinant interleukin-2 (rIL-2) was used to treat 31 patients with progressing metastatic malignant melanoma. Only three patients had disease confined to non-visceral sites; the median number of organ sites involved was four. The first dose of rIL-2 was given intrasplenically (to stimulate cytotoxic cells in high concentration) via a femoral artery catheter, and four further i.v. doses were given over 6 days. A total of three courses at 21-day intervals was planned. Doses were escalated in 15 patients from 1 x 10(6) to 16.4 x 10(4) Cetus units m-2. The maximum tolerated dose (11.0 x 10(6) U m-2) was used in the other 16 patients. Of the 71 courses, severe but transient toxicity requiring interruption of rIL-2 or additional care occurred on three courses (dyspnoea) and 15 from hypotension, but the patients' performance status improved. Four patients had partial tumour responses although in only one patient did response occur in all sites of disease. However, responses occurred in visceral sites and six patients are alive at 9-16 months. IL-2 is of use in advanced melanoma and does not need complicated ICU facilities.

High-dose, double alkylating agent chemotherapy with DTIC, melphalan, or ifosfamide and marrow rescue for metastatic malignant melanoma.

Thirty-seven patients with widely metastatic malignant melanoma were treated with one of three chemotherapy regimens, incorporating high-dose dacarbazine (DTIC). The chemotherapy was followed by autologous bone marrow rescue which was harvested under local anesthesia in 25 of the patients. The three regimens comprised a 24-hour infusion of DTIC (Regimen A for patients less than 45 years of age, 4.3 to 10.5 g/m2; B, if greater than 45 years of age 2.7 to 4.0 g/m2; and later C, if greater than 45 years of age 7.0 to 8.0 g/m2). The second alkylating agent was given at +8 and +16 hours from the start of DTIC. The total doses of the melphalan ranged from 60 to 130 mg/m2 for Regimen A and 30 to 40 mg/m2 for Regimen B. Ifosfamide 5.0 to 8.0 g/m2 was given instead of melphalan in Regimen C. The response rates for the regimens were 81% (25% CR) for A, 27% (11% CR) for B, and 20% (with no complete responders) for Regimen C. There was no statistically significant difference between the three regimens for survival with a median value of 6 months. One of the 16 patients treated with the very high dose Regimen A died of septicemia and three of ten patients in Regimen C died within the first 2 weeks of treatment. There was statistically significant greater myelosuppression, stomatitis, and diarrhea in the very high dosage DTIC and melphalan (Regimen A) compared with the other two regimens. No significant difference in response rate or toxicity was observed for the different dosages escalated within each of the three regimens. Although hematologic and gastrointestinal toxicity were very severe, no unusual side effects were noted except for one episode of severe acute renal failure in the high-dose DTIC and melphalan, Regimen A. Responses occurred mainly in nonvisceral, nodal, and cutaneous sites and occasionally in pulmonary metastases. The Karnofsky performance improved 4 to 6 months after treatment notably with the high-dose DTIC and melphalan therapy. No survival benefit for the combination chemotherapy despite the high dosages was detected and such an approach currently cannot be recommended.