Patients with inflammatory bowel disease and their treating clinicians have different views regarding diet.

BACKGROUND: Diet and body composition play unclear roles in the pathogenesis, activity and symptoms of inflammatory bowel disease (IBD). Evidence-based guidance regarding dietary modification in IBD is lacking. We aimed to determine the attitudes of IBD patients and clinicians to diet. METHODS: The present cross-sectional study comprised an online questionnaire distributed to members of a national IBD patient organisation, assessing demographics, anthropometry, disease phenotype and dietary beliefs. Dietitians, gastroenterologists and surgeons were targeted for a similar questionnaire as a result of membership of national professional bodies. RESULTS: Nine hundred and twenty-eight patients (72.2% female; mean age 39.5 years; age range 5-91 years) responded. Two-thirds of the patients had Crohn's disease. The mean reported body mass index was 24.9 kg m-2 and was significantly skewed to the right. Patients who had taken >10 courses of steroids were had a greater probability of being overweight or obese, independent of disease complications. Most patients (71%) assumed that their diet affected their IBD; 61% considered their IBD specialist disregarded the importance of diet. Of the 136 clinicians who responded, the majority felt that diet was a factor in symptoms and intestinal microbiota. More gastroenterologists (44%) than dietitians (17%) considered that diet had a role in the pathogenesis of IBD (P = 0.003). Twenty-six percent of patients reported receiving dietary advice from their IBD specialist, whereas 98% of gastroenterologists reported advice provision. Patients received diverse advice. Half of the patients followed recommendations provided by a clinician. CONCLUSIONS: The present study demonstrates that IBD patients consider diet to be important in their disease. IBD clinicians from different disciplines have diverse views of the role of diet. Advice given to patients is heterogeneous, often perceived as inadequate and poorly followed.

Changing face of care for patients with moderate to severe inflammatory bowel disease: the role of specialist nurses in the governance of anti-TNF prescribing.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy is highly effective for inflammatory bowel disease (IBD), but expensive and potentially toxic. Meticulous supervision prior to and during anti-TNF treatment is required to screen and monitor patients for adverse clinical events. In addition, a systematic administrative process is necessary to comply with Australian Medicare requirements and ensure ongoing therapy is uninterrupted. IBD nurses are essential components of multidisciplinary IBD services, but their role in facilitating the safe and timely delivery of anti-TNF drugs is unacknowledged. AIM: The aim of the study was to calculate time spent by IBD nurses on anti-TNF drug governance and its indirect cost. METHODS: Time spent on activities related to anti-TNF governance was retrospectively assessed by questionnaire among IBD nurses employed at Melbourne hospitals. The capacity of IBD clinics at these hospitals was separately evaluated by surveying medical heads of clinics. RESULTS: On average, each Melbourne IBD service handled 150 existing and 40 new anti-TNF referrals in 2013. The average annual time spent by nurses supervising an existing and newly referred anti-TNF patient was 3.5 and 5.25 h respectively, or a minimum of two full working days per week. If clinicians undertook this activity during normal clinic time, the organisational opportunity cost was at least 58%. CONCLUSIONS: Anti-TNF therapy governance is an essential quality component of IBD care that is associated with a definite, indirect cost for every patient treated. IBD nurses are best positioned to undertake this role, but an activity-based funding model is urgently required to resource this element of their work.

Clinical selection criteria can predict futile intervention in patients referred for percutaneous endoscopic gastrostomy insertion.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placement is performed in a patient group with high mortality in the short and medium term. For a significant proportion of patients, the procedure provides no increase in survival. There are no standardised assessment tools available to determine the clinical appropriateness of PEG placement, nor any to predict clinical outcome. AIM: The study aims to determine whether clinical assessment, by a trained dietitian, of the appropriateness of PEG placement is predictive of mortality in the short and medium terms. METHODS: A prospective audit was undertaken of all requests for PEG placement at a single large, publicly funded Australian tertiary hospital. The clinical appropriateness of each request was assessed by a trained dietitian, and data on age, sex, reason for referral, comorbidities and satisfaction of assessment criteria were collected, and patient outcome and survival were compared for all patients according to whether a PEG was inserted or not. Main outcome measures were mortality at 30 and 150 days after referral. RESULTS: During the period 2005-2008, 198 patients were referred for PEG; 94 were assessed as appropriate referrals, 104 as inappropriate. Eighty-four patients who underwent gastrostomy, after being assessed as appropriate, had significantly reduced mortality at 30 days (96.4% vs 74.6%, P < 0.0001) and 150 days (82.1% vs 57.9%, P = 0.0001) compared with all other patients. Patients who received PEG despite contrary advice had no significant survival advantage, at 30 days or 150 days, over patients who did not receive PEG. CONCLUSION: The application of selection criteria by trained assessors improves patient selection for PEG insertion and predicts mortality at early and later time points, by identifying patients unlikely to benefit from PEG. The group of patients who received a gastrostomy despite an adverse assessment had no mortality benefit - in these patients, the procedure may have been futile.

Altered glycosylation in donor mice causes rejection of strain-matched skin and heart grafts.

Differential protein glycosylation in the donor and recipient can have profound consequences for transplanted organs, as evident in ABO-incompatible transplantation and xenotransplantation. In this study, we investigated the impact of altered fucosylation on graft acceptance by using donor mice overexpressing human α1,2-fucosyltransferase (HTF). Skin and heart grafts from HTF transgenic mice were rapidly rejected by otherwise completely matched recipients (median survival times 16 and 14 days, respectively). HTF skin transplanted onto mice lacking T and B cells induced an natural killer cell-mediated innate rejection crisis that affected 50-95% of the graft at 10-20 days. However, in the absence of adaptive immunity, the residual graft recovered and survived long-term (>100 days). Experiments using "parked" grafts or MHC class II-deficient recipients suggested that indirect rather than direct antigen presentation plays a role in HTF skin graft rejection, although the putative antigen(s) was not identified. We conclude that altered glycosylation patterns on donor tissue can trigger a powerful rejection response comprising both innate and adaptive components. This has potential implications for allotransplantation, in light of increasing recognition of the variability of the human glycome, and for xenotransplantation, where carbohydrate remodeling has been a lynchpin of donor genetic modification.

Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown. AIMS: The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered. METHODS: All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ(2) tests or Fisher's exact tests. RESULTS: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%). CONCLUSION: Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD.

Primary cytomegalovirus ileitis complicated by massive gastrointestinal haemorrhage in a patient with steroid refractory Crohn's disease.

A young man with known steroid refractory terminal ileal Crohn's disease developed torrential gastrointestinal bleeding necessitating an emergency ileal resection. Serology was indicative of primary cytomegalovirus (CMV) infection and this was confirmed with histopathology of the resected ileum. We highlight the difficulty in clinical practice of distinguishing between CMV infection and CMV disease as well as the different investigations available to aid in the diagnosis of pathogenic CMV disease.

Baboon infant produced by embryo transfer.

An embryo was recovered surgically from a naturally ovulating, naturally inseminated Papio cynocephalus female on day 5 of gestation and transferred surgically to a naturally synchronized, nonmated Papio cynocephalus female on 20 March 1975. A male baboon weighing 875 grams was delivered by cesarean section on 5 September 1975, 174 days after estimated ovulation time.

Low muscle mass at initiation of anti-TNF therapy for inflammatory bowel disease is associated with early treatment failure: a retrospective analysis.

BACKGROUND/OBJECTIVES: Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure. SUBJECTS/METHODS: A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs. Analysis of the images at the third lumbar vertebra was performed using standard techniques to determine cross-sectional areas of skeletal muscle (SM), visceral adipose tissue, subcutaneous adipose tissue and intermuscular adipose tissue. Treatment failure was defined as: post-induction hospital admission or surgery for IBD, escalation of TNF dose or immunosuppressants for clinical LOR, emergence of a new fistula or Crohn's Disease Activity Index (CDAI) >150. RESULTS: Two-thirds of patients had myopenia. Patients with less than gender-specific median SM area had a median time to failure of 520 (s.d. 135) days compared to 1100 (s.d. 151) days for those with more than median SM area (P=0.036). No difference was found in disease duration, inflammatory markers or CDAI between quartiles of SM area. No relation between outcomes and measures of adipose tissue, weight or body mass index was observed. CONCLUSIONS: Identifying low muscle mass at anti-TNF induction as a risk factor for treatment failure may contribute to a more tailored approach to IBD therapy.

Visceral adiposity predicts post-operative Crohn's disease recurrence.

BACKGROUND: Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease. AIM: To determine whether body composition is associated with outcome in a prospective study of post-operative Crohn's disease patients. METHODS: The POCER study evaluated management strategies for prevention of post-operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross-sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area. RESULTS: The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender-specific mean experienced endoscopic recurrence at 18 months (compared to 47%) [relative risk 2.1, 95% CI 1.5-3.0, P = 0.012]. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046). CONCLUSIONS: Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post-operative management strategies.

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

BACKGROUND: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. AIM: To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. METHODS: A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. RESULTS: 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 µg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints-such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. CONCLUSION: Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Review article: acute severe ulcerative colitis - evidence-based consensus statements.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM: To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS: Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS: Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION: These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.

Infection and disease induced in chimpanzees with 6/94, a parainfluenza type 1 virus isolated from human multiple sclerosis brain.

A parainfluenza type 1 virus (6/94) recovered from brain cell cultures of two patients with multiple sclerosis (MS) was inoculated into newborn chimpanzees by the intranasal (IN) or intracerebral (IC) routes. Four of the five animals receiving the virus IN developed clinical signs ranging from mild fever, with or without rhinorrhea, to severe respiratory disease. Two of the chimpanzees died as a result of pneumonia. Virus could be recovered from respiratory tracts for as long as 9 days after exposure and was followed by development of specific neutralizing antibody to the 6/94 virus but not to the HA2 strain of parainfluenza type 1. Brain examination showed astrocytosis, especially of posterior fossa structures, activation of microgliacytes and, in one animal, round cell infiltration of leptomeninges. Of thse three animals receiving virus IC, two developed recurrent seizures beginning 14 months after inoculation. One of these was sacrificed at 23 months of age after progressive neurologic disease, with electroencephalographic abnormalities, developed. The third animal died at 3 months of age of intercurrent pneumonia. No virus was recovered from these animals, although all showed antibody conversion to 6/94 but not HA2 virus. A variety of pathologic lesions were seen in the brains of both animals coming to necropsy particularly in the sacrificed chimpanzee. These included subacute encephalitis, extensive cortical and subcortical degeneration, vascular sclerosis, white matter gliosis and axonal dystrophy.

Health maintenance organizations and medical education: breaking the barriers.

Academic medical centers (AMCs) are under pressure to increase ambulatory medical education, but their capacity for such teaching is limited. Health maintenance organizations (HMOs) are a large and growing institutional setting that could participate in clinical education. Until now, relatively few HMOs and AMCs have reached agreements about teaching, because traditional suspicions have blocked collaboration. Responding to a case prepared as the basis of discussion, about 450 academics and HMO medical directors explored the barriers to and incentives for cooperation between AMCs and HMOs in clinical education. The two groups identified different issues as barriers to collaboration, leaving considerable room to negotiate agreements. AMCs, especially, need to be prepared to offer meaningful academic and financial inducements to attract HMOs to participate in teaching.

The influence of the New Pathway curriculum on Harvard medical students.

BACKGROUND: This study evaluated the effect of a radically redesigned curriculum at Harvard Medical School on preclinical students' knowledge, skills, personal characteristics, approaches to learning, and educational experiences. METHOD: Multiple measures were used to collect data from 121 students from the entering classes of 1989 and 1990 who had been randomly assigned to the New Pathway or traditional curricula; all had applied to be in the new curriculum. RESULTS: The New Pathway students reported that they learned in a more reflective manner and memorized less than their control counterparts in the traditional curriculum during the preclinical years. The New Pathway group preferred active learning and demonstrated greater psychosocial knowledge, better relational skills, and more humanistic attitudes. They felt more challenged, had closer relationships with faculty, and were somewhat more anxious than those in the traditional program. There was no difference in problem-solving skills or biomedical knowledge base. CONCLUSION: Students in the new curriculum learned differently, acquired distinctive knowledge, skills, and attitudes, and underwent a more satisfying and challenging preclinical medical school experience without loss of biomedical competence. These findings should encourage other schools to consider such a curriculum.

The "teaching HMO": a new academic partner.

Health care reform is a potential threat to the academic missions of medical schools and academic health centers. But managed care, the source of much of their concern, may also represent a way for medical schools to improve their future academic outcomes. Harvard Medical School and the Harvard Community Health Plan, a large health maintenance organization (HMO) in greater Boston, recently formed the first medical school department to be based in a freestanding HMO. This arrangement is an example of a model that replicates, in a managed care organization, the long-standing and highly successful teaching hospital academic structure in academic medical centers. The authors describe this model in detail, show how the Harvard collaboration works, and explain the benefits each institution saw in creating a joint entity, the rationale for making that new entity an academic department, and the implications for other academic health centers. They conclude that the Harvard experience shows that alliances between medical schools and large HMOs can create vibrant practice settings for teaching and research in academic areas (such as prevention and primary care medicine) that have been relatively neglected in recent times, and that the "teaching HMO" may have the potential to transform academic medicine in the next century just as the teaching hospital transformed it in this century.

Long-term outcomes of the New Pathway Program at Harvard Medical School: a randomized controlled trial.

PURPOSE: To evaluate the long-term effects of an innovative curriculum, the New Pathway (NP) Program, on behaviors and attitudes related to humanistic medicine, lifelong learning, and social learning. METHOD: Long-term follow-up of Harvard Medical School students who participated in a randomized controlled trial. Descriptive study using 1998 telephone interviews of 100 1989 and 1990 graduates (50 who had studied the NP curriculum, 50 who had studied the traditional curriculum). The NP Program consisted of problem-based learning tutorials, with coordinated lectures, labs, experiences in humanistic medicine, and clinical experiences; the traditional program consisted of basic science lectures and labs. RESULTS: Of 22 measures on the survey, NP and traditional students differed significantly on only five (three humanism; two social learning): 40% of NP students and 18% of traditional students went on to practice primary care or psychiatry. NP students rated their preparation to practice humanistic medicine higher than did traditional students and expressed more confidence in their ability to manage patients with psychosocial problems. NP students were more likely than were traditional students to believe that faculty from the first two years continued to influence their thinking. NP students liked the pedagogic approaches of their program more than traditional students did. There was no difference between the groups on measures of lifelong learning. CONCLUSIONS: Differences between NP and traditional students in the humanism domain first appeared during medical school and residency and remained significant well into practice, suggesting that humanistic medicine can be taught and learned.

Will the power of the marketplace produce the workforce we need?

The medical manpower market will work best as an agent for change in primary care when there is vigorous demand, a sophisticated buyer, and not too large a gap to fill--conditions that we can expect with managed care growth in U.S. urban settings in the next decade. In these circumstances, the primary care supply will adjust without the need for regulatory intervention. The most dramatic workings of the market will be in stripping from the system the excess payments for practicing subspecialist physicians. However, market forces will not quickly moderate the growing oversupply of doctors nor their maldistribution to areas of need. Focused public policy manpower interventions will be needed to correct these deficits quickly.