Alexandra Gorelik

Crohn's disease management after intestinal resection: a randomised trial.

BACKGROUND Most patients with Crohns disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. METHODS In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohns disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patients study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. FINDINGS Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively. INTERPRETATION Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohns disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring. FUNDING AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohns Colitis Australia, and the National Health and Medical Research Council.

Prospective Characterization of Catheter–Tissue Contact Force at Different Anatomic Sites During Antral Pulmonary Vein Isolation

Background— Catheter–tissue contact is critical for effective lesion creation. We characterized the contact force (CF) at different anatomic sites during antral pulmonary vein (PV) isolation for atrial fibrillation. Methods and Results— Two experienced operators performed PV isolation in 22 patients facilitated by a novel CF-sensing ablation catheter in a blinded fashion. Average CF and force-time integral data from 1602 lesions were analyzed. The left and right PV antra were divided into the following: carina, superior, inferior, anterior, and posterior quadrants for analysis. There was significant variability in CF within and between different PV quadrants (P<0.05). Lowest CF of all left PV sites was at the carina and anterior quadrant, whereas highest CF was at the superior and inferior quadrants (P<0.05). Lowest CF of all right PV sites was at the carina, whereas highest CF was at the anterior and inferior quadrants (P<0.05). When comparing similar PV quadrants on the left versus right (eg, left carina versus right carina), CF was always higher in the right PVs (P<0.05), except at the superior quadrant where CF was similar in the left and right PVs (P=0.19). There was no specific pattern of anatomic distribution of excess CF (P=0.39). Conclusions— Monitoring of catheter–tissue CF during PV isolation demonstrates significant variability in CF within and between different PV antral sites. Sites of lowest CF were the carina and anterior left PVs and the carina of the right PVs. This information may be important for improving ablation efficacy and clinical outcomes during PV isolation.

Falls and fractures in patients chronically treated with antiepileptic drugs

Objective: To evaluate fractures and falls in epilepsy patients taking antiepileptic drugs (AED) and to assess their awareness of AED-related bone health, falls, and fracture risk. Methods: A cross-sectional study was conducted in epilepsy patients taking AEDs and in nonepileptic non-AED users. Information on falls and fracture history was collected. Results: A total of 150 AED users were compared with 506 non-AED users. Users had greater odds of fracture at spine (odds ratio [OR] 3.92; confidence interval [CI] 1.08–14.16; p = 0.037), clavicle (OR 3.75; CI 1.24–11.34; p = 0.019), and ankle sites (OR 2.34; CI 1.01–5.42; p = 0.048), increased odds for osteoporosis (OR 4.62; CI 1.40–15.30; p = 0.012), and fracture occasions (OR 2.64; CI 1.29–5.43; p = 0.008). We estimate that with every year of AED use the odds of fractures increase by 4%–6%, or 40% per decade for any fracture (OR 1.40; CI 1.02–1.91) and 60% for seizure-related fractures (OR 1.63; CI 1.10–2.37). Non-seizure-related fractures (69% of cumulative fractures) occurred more than seizure-related fractures during therapy. Female users, compared to female nonusers, had more non-seizure falls (31% vs 17%, p = 0.027) and multiple falls (18% vs 5%, p = 0.028) in the preceding year. Fewer than 30% of epilepsy patients knew of the association of AED use with increased risk for fractures, decreased bone mineral density, or falls. Conclusions: Epilepsy patients taking AEDs had a higher risk of fractures, which was highest in those with longer-term AED exposure. Female AED users had a higher prevalence of falls than matched nonusers. Awareness among epilepsy patients regarding risks of falling and fractures was low.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high‐risk patients – a POCER study analysis

Crohns disease recurs in the majority of patients after intestinal resection.

IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low‐grade gliomas

The isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most common mutation in World Health Organization (WHO) grade II gliomas, reported to be expressed in 70–80%, but only 5–10% of high grade gliomas. Low grade tumors, especially the protoplasmic subtype, have the highest incidence of tumor associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2‐hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a role in the pathogenesis of TAE in low grade gliomas.

Hepatic macrophage activation predicts clinical decompensation in chronic liver disease

Hepatic macrophages (Kupffer cells) play important roles in inflammation and portal hypertension in patients with chronic liver disease (CLD).1 We recently showed that plasma soluble CD163 (sCD163), a specific marker for macrophage activation, is produced within and released from the liver with a direct relationship to the portal venous pressure gradient.2 ,3 We hypothesised that: (1) sCD163 is elevated in patients with CLD with previous clinical decompensation; and (2) sCD163 is a marker for CLD progression and clinical deterioration. We measured sCD163 in 52 controls and 116 consecutive patients with CLD (89% cirrhosis) caused by chronic hepatitis C (36%), alcohol (30%), non-alcoholic fatty liver disease (11%), chronic hepatitis B (10%); other liver diseases (12%) accounted for the remainder of the cases. Cirrhosis was diagnosed by consistent examination and radiological findings, or by liver biopsy. All controls had no history or clinical examination signs of CLD, and normal liver function tests. They were followed for a median of …

Patients Who Leave Without Being Seen in Emergency Departments: An Analysis of Predictive Factors and Outcomes

OBJECTIVES The objective was to identify predictive factors and outcomes associated with patients who leave emergency departments (EDs) without being seen in Victoria, Australia. METHODS This was a retrospective observational study of Victorian ED patient visits between July 1, 2000, and June 30, 2005, using linked hospital, ED, and death registration data. Index ED visits were identified for patients who left without being seen (LWBS) and for those who completed ED treatment and were discharged home. Statistical analyses included a general description and univariate analysis of patient, ED visit, temporal, and hospital-level factors. Logistic regression models were developed to assess risk factors associated with LWBS status compared to patients who completed treatment, to assess 48 hour re-presentations to ED; 48-hour hospital admissions; and 2-,7-, and 30-day mortality among those who LWBS compared to those who completed treatment. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) are presented. RESULTS There were 239,305 LWBS episodes, for 205,500 patients over the 5-year period. Independent factors associated with LWBS patients in comparison to those who completed treatment include patients who are younger (15 to 24 years, OR = 2.46, 99% CI = 2.37 to 2.56), male (OR = 1.07, 99% CI = 1.05 to 1.08), of Australian indigenous background (OR = 1.63, 99% CI = 1.53 to 1.73), of non-English-speaking background (OR = 1.08, 99% CI = 1.06 to 1.10), noncompensable status (OR = 1.73, 99% CI = 1.68 to 1.79), self-referring (OR = 1.46, 99% CI = 1.43 to 1.49), nonassisted arrival mode (OR = 1.35, 99% CI = 1.30 to 1.40), and those with a hospital admission in the 12 months before the ED presentation (OR = 1.53, 99% CI = 1.51 to 1.55). Patients who LWBS had triage categories of lower urgency (nonurgent, OR = 8.21, 99% CI = 8.00 to 8.43), attended during the evening (OR = 1.10, 99% CI = 1.08 to 1.12), on either Sunday (OR = 1.20, 99% CI = 1.18 to 1.23) or Monday (OR = 1.20, 99% CI = 1.17 to 1.23), in winter (OR = 1.14, 99% CI = 1.12 to 1.16), with higher rates occurring in higher volume EDs (OR = 2.20, 99% CI = 2.15 to 2.26). There was no greater risk of mortality for LWBS patients compared to patients who completed treatment. The risk of hospital admission within 48 hours of discharge was lower for LWBS patients (OR = 0.60, 99% CI = 0.58 to 0.62); however, ED re-presentation risk was higher (OR = 1.63, 99% CI = 1.60 to 1.67). CONCLUSIONS Patients who leave EDs in Victoria, Australia, without being seen are at lower risk of hospital admission and at no greater risk of mortality, but are at higher risk of re-presenting to an ED compared to patients who complete treatment and are discharged home.

Use of antipsychotic medications for the management of delirium: an audit of current practice in the acute care setting

OBJECTIVE Despite delirium being common in older hospitalized people, little is known about its management. The aims of this study are (1) to describe the pharmacological management of delirium in an acute care setting as a baseline measure prior to the implementation of newly developed Australian guidelines; and (2) to determine what areas of delirium pharmacological management need to be targeted for future practical guideline implementation and quality improvement activities. METHODS A medical record audit was conducted using a structured audit form. All patients aged 65 years and over who were admitted to a general medical or orthopaedic unit of the Royal Melbourne Hospital between 1 March 2006 and 28 February 2007 and coded with delirium were included. Data on the use of antipsychotic medications for the management of delirium in relation to best practice recommendations were assessed. RESULTS Overall 174 episodes of care were included in the analysis. Antipsychotic medications were used for the management of most patients with severe behavioral and or emotional disturbance associated with delirium. There was variation in the prescribing patterns of antipsychotic agents and the documentation of medication management plans. Less than a quarter of patients prescribed antipsychotic medication were started on a low dose and very few were reviewed on a regular basis. CONCLUSION A wide range of practice is seen in the use of antipsychotic agents to manage older patients with severe symptoms associated with delirium. The findings highlight the need to implement evidence-based guideline recommendations with a focus on improving the consistency in the pharmacological management and documentation processes.

Vitamin D Status, Bone Mineral Density and Mental Health in Young Australian Women: The Safe-D Study

Background. Vitamin D deficiency has been associated with both poor bone health and mental ill-health. More recently, a number of studies have found individuals with depressive symptoms tend to have reduced bone mineral density. To explore the interrelationships between vitamin D status, bone mineral density and mental-ill health we are assessing a range of clinical, behavioural and lifestyle factors in young women (Part A of the Safe-D study). Design and methods. Part A of the Safe-D study is a cross-sectional study aiming to recruit 468 young females aged 16-25 years living in Victoria, Australia, through Facebook advertising. Participants are required to complete an extensive, online questionnaire, wear an ultra-violet dosimeter for 14 consecutive days and attend a study site visit. Outcome measures include areal bone mineral measures at the lumbar spine, total hip and whole body, as well as soft tissue composition using dual energy x-ray absorptiometry. Trabecular and cortical volumetric bone density at the tibia is measured using peripheral quantitative computed tomography. Other tests include serum 25-hydroxyvitamin D, serum biochemistry and a range of health markers. Details of mood disorder/s and depressive and anxiety symptoms are obtained by self-report. Cutaneous melanin density is measured by spectrophotometry. Expected impact. The findings of this cross-sectional study will have implications for health promotion in young women and for clinical care of those with vitamin D deficiency and/or mental ill-health. Optimising both vitamin D status and mental health may protect against poor bone health and fractures in later life. Significance for public health Vitamin D deficiency, depression and osteoporosis are all major public health issues. Vitamin D deficiency has been associated with both reduced bone mineral density and depressive symptoms. Moreover, cohort studies have found that subjects with depression have lower bone mineral density when compared to healthy controls. Early adulthood is a critical time in young woman’s lives as their independence, behaviours and lifestyle choices are established. These choices made as a young adult lay down the foundation for future health trajectories for not only for themselves but also for their potential partners and families. Addressing vitamin D deficiency, poor bone health and mental ill-health at a younger age may ultimately improve their wellbeing, productivity and long-term health outcomes. This study is of particular significance as the interplay between vitamin D, depression and bone health is currently uncertain and such knowledge is crucial for understanding, prevention and treatment of these conditions.

Redesigning care for chronic conditions: improving hospital-based ambulatory care for people with osteoarthritis of the hip and knee.

Background: Osteoarthritis of the hip and knee is a highly prevalent chronic condition in Australia that commonly affects older people who have other comorbidities. We report the pilot implementation of a new chronic disease management osteoarthritis service, which was multidisciplinary, evidence‐based, supported patient self‐management and care coordination.