Definitions of remission in psoriasis: a systematic literature review from the National Psoriasis Foundation.

Psoriasis studies increasingly employ outcomes that indicate complete disease resolution, yet remission and cure are poorly defined for psoriasis. We conducted a systematic literature review to identify definitions of psoriasis remission and cure reported in the literature. Medline, EMBASE, and The Cochrane Central Register of Controlled Trials databases were searched on July 22, 2020, for full-text studies providing definitions for psoriasis remission/cure. Definitions were analysed descriptively for endpoint, time-frame, on/off treatment, patient-reported outcomes, and disease domains. We identified 106 studies that provided 41 unique remission definitions. Most definitions included endpoints based on Psoriasis Area and Severity Index (PASI), such as PASI75 (n = 16 studies), PASI90 (n = 10), PASI100 (n = 10), and PASI of 0 (n = 3), and descriptive endpoints related to 'skin clearance' (n = 18). Few definitions specified time-frame, on/off treatment or other psoriasis-related disease domains. One small consensus-initiative defined drug-free remission for plaque psoriasis by BSA of 0 without any therapy for at least 12 months. While there is no cure for psoriasis, seven studies defined psoriasis cure using similar endpoints to those used to define remission. We identified a variety of definitions of psoriasis remission. These results will inform the development of consensus-based definitions for psoriasis remission to support efforts to improve research and clinical outcomes.

Perspectives of paediatric and adult gastroenterologists on transfer and transition care of adolescents with inflammatory bowel disease.

BACKGROUND: Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking. AIM: We aimed to explore the perceived needs of adolescents with IBD among paediatric and adult gastroenterologists and to identify barriers to effective transition. METHODS: A web-based survey of paediatric and adult gastroenterologists in Australia and New Zealand employed both ranked items (Likert scale; from 1 not important to 5 very important) and forced choice items regarding the importance of various factors in facilitating effective transition of adolescents from paediatric to adult care. RESULTS: Response rate among 178 clinicians was 41%. Only 23% of respondents felt that adolescents with IBD were adequately prepared for transition to adult care. Psychological maturity (Mean = 4.3, standard deviation (SD) = 0.70) and readiness as assessed by adult caregiver (Mean = 4, SD = 0.72) were prioritised as the most important factors in determining timing of transfer. Self-efficacy and readiness as assessed by adult caregiver were considered the two most important factors to determine timing of transition by both groups of gastroenterologists. Poor medical and surgical handover (Mean = 4.10, SD = 0.8) and patients' lack of responsibility for their own care (Mean= 4.10, SD = 0.82) were perceived as major barriers to successful transition by both paediatric and adult gastroenterologists. CONCLUSIONS: Deficiencies exist in current transition care of adolescents with IBD in Australia and New Zealand. Standardising transition care practices with strategies aimed at optimising communication, patient education, self-efficacy and adherence may improve outcomes.

Postoperative recurrence of Crohn's disease: impact of endoscopic monitoring and treatment step-up.

AIM: Eighty per cent of patients with Crohn's disease require surgery, of whom 70% will require a further operation. Recurrence occurs at the anastomosis. Although often recommended, the impact of postoperative colonoscopy and treatment adjustment is unknown. METHOD: Patients with a bowel resection over a 10-year period were reviewed and comparison made between those who did and did not have a postoperative colonoscopy within 1 year of surgery, and those who did or did not have a step-up in drug therapy. RESULTS: Of 222 patients operated on, 136 (65 men, mean age 33 years, mean disease duration 8 years, median follow-up 4 years) were studied. Of 70 patients with and 66 without postoperative colonoscopy, clinical recurrence occurred in 49% and 48% (NS) and further surgery in 9% and 5% (NS). Eighty-nine per cent of colonoscoped patients had a decision based on the colonoscopic findings: of these, 24% had a step-up of drug therapy [antibiotics (n =10), aminosalicylates (n=2), thiopurine (n=5), methotrexate (n=1)] and 76% had no step-up in drug therapy. In colonoscoped patients clinical recurrence occurred in 9 (60%) of 15 patients with, and 23 (49%) of 47 without step-up and surgical recurrence in 2 (13%) of 15 and 4 (9%) of 47 (NS). CONCLUSION: Clinical recurrence occurs in a majority of patients soon after surgery. In this cohort, there was no clinical benefit from colonoscopy or increased drug therapy within 1 year after operation. However, the response to the endoscopic findings was not standardized and immunosuppressive therapy was uncommon. Standardizing timing of colonoscopy and drug therapy, including more intense therapy, may improve outcome, although this remains to be proven.

Gastroenterology training in Australia: how much is enough?

BACKGROUND: Advanced training in gastroenterology currently consists of 2 years of core training and 1 elective (non-core) year. We surveyed gastroenterologists 2-7 years following completion of training to determine the strengths and weaknesses of their training. METHODS: All gastroenterologists were invited to participate in an anonymous online survey. RESULTS: There was a 46% response rate (49/110). Eighty-one per cent were male with most aged 36-45. Respondents felt that the current training programme prepared them well for public practice and endoscopy but less well for private practice, ambulatory care, surgical aspects of gastroenterology and functional gastrointestinal disorders. Most had faced challenges transitioning to consultant practice. The majority (53%) spent more than the standard 3 years to complete training in gastroenterology. The top three subspecialty Fellowships were in endoscopy (45%), inflammatory bowel disease (29%) and hepatology (23%). In their elective year, 42% undertook a predominantly clinical year (registrar-type position in general or subspecialty gastroenterology), 28% engaged in research while 24% trained in another specialty. Seventy-eight per cent were in full-time work, and 36% were supervising trainees. Ninety-eight per cent felt that it was beneficial for trainees to move between hospitals during the core years of their advanced training. CONCLUSIONS: The current Australian gastroenterology training programme is generally adequate in preparing trainees for consultant practice but could be improved by increased emphasis on areas such as private practice, ambulatory gastroenterology and functional gastrointestinal diseases. Exposure to a variety of experiences by training in several different hospitals during core training was universally viewed as being important.

A plastic scintillator and HPGe ß-γ coincidence detection system.

A network of specialist laboratories support the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) with re-measurements of radionuclide samples, including xenon gas. The measurement of four xenon fission product radionuclides (133Xe, 135Xe, 131mXe and 133mXe) can be used to detect an underground nuclear explosion. Laboratories use a range of techniques to measure the radionuclides, including beta-gamma (ß-γ) coincidence spectrometry. These highly-sensitive measurements are capable of detecting concentrations of down to 500 atoms of 133Xe in a few cm3 of xenon. In some detector systems, detection of the metastable isomers (131mXe and 133mXe) can be more challenging due to interferences between the signatures of different radionuclides. Recent work has shown that using high-purity Germanium (HPGe) high-resolution gamma detectors, these interferences can be reduced, lowering the dependence of the detection limits on radionuclide sample isotopic composition. One downside of these detectors is the reduction in detection efficiency, which impacts the overall detection sensitivity; so assessing different detector systems is a priority for radionuclide laboratories. This work presents a coincidence detector system comprising of a plastic scintillator gas cell and a large-crystal high-purity germanium detector. The energy resolution, coincidence detection efficiency, MDA and interference factors are determined from measurements of synthetic radioxenon gas samples.

Assessment of chronic hepatitis B: the importance of hepatitis B virus DNA testing.

BACKGROUND: Chronic hepatitis B (CHB) has an estimated prevalence of 90 000 to 160 000 in Australia. Cirrhosis and hepatocellular carcinoma are important complications of CHB and appropriate evaluation of hepatitis B surface antigen (HBsAg)-positive individuals is vital to identify treatment candidates. METHODS: A review of the database of a tertiary hospital was performed and 348 HBsAg-positive individuals with baseline demographic, virological, serological and biochemical variables were identified and evaluated cross-sectionally. A small subgroup of hepatitis B e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) at baseline were identified and followed longitudinally. RESULTS: 175/348 (50%) of patients were in the HBeAg-negative, chronic hepatitis phase of disease, 22% in the HBeAg-positive immune clearance and 6% in the immune tolerant phases. HBeAg-negative patients were older and more likely to be male than HBeAg-positive patients. The correlation between hepatitis B virus (HBV) DNA and ALT levels was examined. ALT and HBV DNA levels showed no correlation in HBeAg-positive CHB and only a weak correlation in HBeAg-negative patients. Furthermore, 35% of HBeAg-negative patients with detectable HBV DNA had a normal ALT. Conversely 38% of HBeAg-negative patients with no detectable HBV DNA had an elevated ALT. A persistently normal ALT over 24 months was seen in five of nine HBeAg-negative patients with normal initial ALT and detectable HBV DNA. CONCLUSION: Appropriate evaluation of HBeAg-negative CHB must include HBV DNA because the ALT is not a reliable guide to underlying viral replication.

Gastroenterology training in Australia: a perspective from the coal face.

BACKGROUND: The Royal Australasian College of Physicians is developing curricula for training. AIMS: We surveyed gastroenterology trainees on their training experience to establish whether training needs were being met. METHODS: An online anonymous survey of all gastroenterology trainees in 2009. RESULTS: Ninety-one per cent of trainees responded (105/115). Of these, 92% were adult, and 8% were paediatric trainees. Seventy four were core, and 31 were noncore trainees. Of those who had completed core training, the majority (86%) felt that their training had prepared them adequately for independent practice as a gastroenterologist. However, most respondents felt that core advanced training should be 3 years instead of 2 years. The majority (86%) saw a benefit in moving between hospitals during core training. Of the trainees managing inpatients, 57% were managing 10 or more per day, and 63% had three or more consultant ward rounds per week. The top three noncore fellowships were advanced endoscopy (44%), hepatology (28%) and inflammatory bowel disease (17%). Sixty-one per cent and 39% were undertaking a clinical and research fellowship respectively. Seventy-two per cent of core trainees attended up to three endoscopy lists per week, and 76% were on the on-call urgent endoscopy roster. For on-call endoscopy, 27% of third-year noncore trainees and 5% of core trainees were unsupervised. CONCLUSIONS: The majority of trainees felt that their core training would prepare them adequately for independent practice as gastroenterologists. Overall, trainees valued movement between hospitals during training and felt that core training should be 3 years. Some trainees had inadequate consultant support for out-of-hours emergency endoscopy.

Cadmium-113 nuclear magnetic resonance studies of bovine insulin: two-zinc insulin hexamer specifically binds calcium.

By use of cadmium-113 nuclear magnetic resonance spectroscopy, a specific calcium ion binding site has been identified in the bovine two-zinc insulin hexamer. This site is composed of six glutamyl carboxylate groups clustered in the center of the hexamer, and is distinct from the normal zinc ion binding sites.

Sarcina-like bacteria associated with bloat in young lambs and calves.

Sarcina species are fastidious Gram-positive anaerobic bacteria that occur in cubical packets of eight or more cells. In 2006 to 2007, they were associated with cases of acute abomasal bloat in young lambs and calves. Two incidents were in lambs aged three to six weeks that were found dead, with one or two cases in each of a group of 15 and 100 lambs. Three incidents were recorded in small groups of calves up to 10 days of age, two cases in each incident, with the calves found dead or dying after a short illness characterised by bloat. Their gross lesions included emphysema and oedema of the abomasal wall, mucosal hyperaemia and haemorrhage, and rupture of the abomasum. Histological lesions included abomasitis with congestion, haemorrhage, emphysema and oedema. Bacteria characteristic of Sarcina species were observed in sections associated with the superficial mucosa of these cases, but the bacteria were not detected in cultures.

Chronic hepatitis B: recommendations for therapy based on the natural history of disease in Australian patients.

BACKGROUND: Chronic hepatitis B infection (CHB) is a major health problem in Australia and worldwide. CHB is associated with significant long-term morbidity and mortality. Well tolerated treatment is now available, however the development of resistance is common and the optimal timing of treatment is yet to be determined. Identifying the factors that influence the natural history of CHB may help determine which patients need treatment and when to start it. OBJECTIVE: To determine the demographics, clinical features and virological profile of Australian patients infected with CHB and the influence of these factors on disease activity and severity. STUDY DESIGN: Review of prospectively collected demographic, clinical and virological features of all patients positive for hepatitis B surface antigen (HBsAg) for more than 6 months who were referred to St. Vincent's Hospital liver clinics. Age, sex and ethnicity were correlated with hepatitis B e antigen status (HBeAg), HBV replication status (ALT and HBV DNA), genotype and liver histology. RESULTS: 703 chronic hepatitis B surface antigen positive patients were identified. The patients were predominantly male with an average age of 44. Eighty two percent of patients were born overseas, primarily from Asian (65%) and Mediterranean countries (14%). Two thirds (426) had an elevated ALT (median 79) at presentation. HBeAg was positive in 37%. Active viral replication, defined as abnormal ALT or positive HBVDNA, was present in 74%, 48% of whom were HBeAg negative. In a subset of 103 patients genotyped, 8% had genotype A, 29% B, 41% C and 22% D. Genotype correlated with ethnicity; patients infected with genotypes A were predominantly Caucasian, B and C were Asian, and D were Mediterranean. Of 296 (42%) patients who underwent liver biopsy, 76 (27%) had advanced fibrosis. Advanced fibrosis was associated with increasing age and Mediterranean ethnicity. CONCLUSION AND RECOMMENDATIONS: Perinatal or early childhood transmission is predominant mode of infection in Australia. Two thirds of this cohort had active replication and were at increased risk of developing cirrhosis and/or hepatoma. Advanced disease was associated with age and ethnicity. HBeAg negative CHB accounts for almost half of all those with active viral replication. This parallels the rise in this form of CHB in Asia and the Mediterranean basin. Screening should be offered to people born in, or with parents born in areas of high endemnicity. To detect the development of active disease, patients with positive HBsAg but normal ALT should have liver function tests done 6 monthly and those with elevated ALT should be referred for consideration of therapy, irrespective of HBeAg status.

The relationships between IFNL4 genotype, intrahepatic interferon-stimulated gene expression and interferon treatment response differs in HCV-1 compared with HCV-3.

BACKGROUND: The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. AIM: We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. METHODS: HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. RESULTS: Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r(2) = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. CONCLUSIONS: The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype.

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

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.

OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.

Correlation of chi orientation with transcription indicates a fundamental relationship between recombination and transcription.

Cross-over hot-spot instigator (Chi) sequences (5'-GCTGGTGG-3') are abundant, strand-specific, sequences, which locally increase recombination in Escherichia coli. Located within G-rich 'recombination islands', Chi orientations correlate with the orientations both of DNA replication and of transcription. Consistent with evidence from eukaryotic systems for a fundamental relationship between recombination and transcription, we find for E. coli Chi sequences, and for Haemophilus influenzae Chi-like sequences, that orientations correlate better with transcription than with replication. Complying with Szybalski's transcription direction rule, open reading frames in these prokaryotes have purine-rich mRNA-synonymous DNA strands. Hence, the G-richness of 'recombination islands' may reflect their correspondence with 'transcriptional islands' (genes). Comparison of a natural with the corresponding shuffled sequence, indicates a base order-dependent island unit of approx. 1kb. 1998 Elsevier Science B.V.

Plasma lipid changes after supplementation with beta-glucan fiber from yeast.

BACKGROUND: Dietary fiber has been shown to improve blood lipids. OBJECTIVE: The purpose of this study was to evaluate the effect on serum lipids of a yeast-derived beta-glucan fiber in 15 free-living, obese, hypercholesterolemic men. DESIGN: After a 3-wk period in which subjects ate their usual diet, 15 g fiber/d was added to the diet for 8 wk and then stopped for 4 wk. Plasma lipids were measured weekly during baseline and at week 7 and 8 of fiber consumption, and again at week 12. RESULTS: Compared with baseline, fiber consumption significantly reduced plasma total cholesterol (by 8% at week 7 and 6% at week 8; P < 0.05 using Bonferroni correction); week 12 values did not differ from baseline. No significant differences were noted between baseline LDL cholesterol and values at weeks 7, 8, or 12 when comparing individual groups by using Bonferroni correction, even though the overall one-way analysis of variance with repeated measures was highly significant (P < 0.001). LDL-cholesterol concentrations did decline by 8% at week 8 compared with baseline. There was a significant effect of diet on plasma HDL-cholesterol concentrations (P < 0.005 by one-way ANOVA with repeated measures). However, a group difference was observed only between baseline and week 12 (16% increase; P < 0.05 by Bonferroni correction). Triacylglycerol concentrations did not change. CONCLUSIONS: The yeast-derived beta-glucan fiber significantly lowered total cholesterol concentrations and was well tolerated; HDL-cholesterol concentrations rose, but only 4 wk after the fiber was stopped.

Review article: the clinical role of anti-TNFalpha antibody treatment in Crohn's disease.

The recent licensing of anti-TNFalpha antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically-engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long-term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application.

Evaluation of Helicobacter species in inflammatory bowel disease.

BACKGROUND: Bacteria have been implicated in the pathogenesis of inflammatory bowel disease. Helicobacter species have been shown to cause colitis in animal models and have been identified in human diarrhoeal illness and Crohn's disease. AIM: To determine whether Helicobacter species are present in human inflammatory bowel disease tissue. METHODS: Thirty patients undergoing colonoscopy for clinical reasons were studied. Nine had Crohn's disease, 11 had ulcerative colitis and 10 had histologically normal colons. Tissue was snap-frozen at -70 degrees C. DNA was extracted and examined by five different polymerase chain reaction (PCR) assays that were either genus or species specific for Helicobacter. RESULTS: Analyses of colonic biopsies by two Helicobacter genus-specific PCR assays, two H. pylori-specific assays and a PCR assay designed to amplify fragments of 'H. heilmannii'-like organisms demonstrated that product was not generated by any test. Internal control PCR demonstrated that PCR results for the five assays were not negative due to the presence of residual substances inhibitory to PCR. CONCLUSIONS: Helicobacter species were not identified in this study, using multiple PCRs to eliminate the problems of non-specific cross-reaction. This suggests that Helicobacter species do not play a role in the pathogenesis of inflammatory bowel disease.