Week 4 viral load predicts long-term suppression of hepatitis B virus DNA during antiviral therapy: improving hepatitis B treatment in the real world.

BACKGROUND: Entecavir and tenofovir potently suppress hepatitis B virus (HBV) replication so that serum HBV DNA levels <20 IU/mL can be achieved after 2 years. Despite this, inadequate suppression is reported in >20% of cases for unclear reasons. AIM: We tested whether 4-week viral load (VL) assessment could improve 96-week treatment outcome. METHODS: Data on all chronic hepatitis B patients treated with entecavir or tenofovir between 2005 and 2014 were entered prospectively. Full data capture included pre-treatment, weeks 4, 24, 48 and 96 HBV DNA titre, HBeAg, age, gender, antiviral agent and dose escalation. Compliance data were compiled from pharmacy records, doctors' letters and clinic bookings/attendance. Time to achieve complete viral suppression (HBV DNA < 20 IU/mL) was graphed using Kaplan-Meier curves. Factors affecting this were examined using a multivariate Cox Proportional Hazard model. RESULTS: Among 156 patients treated, 72 received entecavir and 84 tenofovir. Pre-treatment HBV DNA titre, 4-week assessment and compliance impacted significantly on time to complete viral suppression. At 96 weeks, 90% of those assessed as compliant by 4-week HBV DNA had complete viral suppression versus 50% followed by 6-month VL estimation. Continuing care by the same physician was related to 4-week VL testing and optimal compliance. CONCLUSIONS: Medium-term outcomes of HBV antiviral therapy are improved by early on-treatment VL testing, facilitating patient engagement and improved compliance. The observation that 90% complete viral suppression after 2 years monotherapy is achievable in a routine clinic setting questions the need for combination therapy in HBV cases with suboptimal response.

A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

AIMS: To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. METHODS: A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. RESULTS: Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. CONCLUSIONS: We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control.

Spondyloarthropathy in inflammatory bowel disease patients on TNF inhibitors.

BACKGROUND: Musculoskeletal symptoms are the most common extra-intestinal manifestation associated with inflammatory bowel disease (IBD). Spondyloarthritis (SpA) is an umbrella term applied to a group of rheumatic diseases with some features in common and others distinct from other inflammatory arthritides. AIM: To determine self-reported prevalence of SpA associated musculoskeletal manifestations in an IBD cohort on tumour necrosis factor (TNF) inhibitors using a questionnaire incorporating Assessment of SpondyloArthritis International Society (ASAS) criteria. METHODS: Consecutive IBD patients on TNF inhibitors attending a single IBD centre (May-September 2011) were asked to complete a SpA questionnaire. Data collected included SpA and IBD variables, demographics, concurrent medications, co-morbidities and autoimmune serology. RESULTS: The 140-patient cohort included 96 suffering from Crohn disease and 44 from ulcerative colitis. The mean age of disease onset was 29.3 years and 45% were men. Concurrent or past history of inflammatory back pain was reported by 29% subjects. Using the imaging and clinical arms of the ASAS criteria, 30% and 14% subjects respectively had axial SpA. Arthritis was reported by 34%, enthesitis 17%, dactylitis 4%, uveitis 6%, psoriasis 6% and a family history of SpA in 39%. Peripheral SpA was present in 41% by the ASAS criteria. There were no differences in these frequencies between Crohn disease and ulcerative colitis. A positive antinuclear antibodies (>1:80) was found in 19% before commencement of TNF inhibitor therapy and increased to 78% on therapy. Clinical drug-induced lupus erythematosus was uncommon (4%) and was characterised by new clinical signs and symptoms, including arthralgia, rash with elevated dsDNA titres and positive antinuclear antibodies. CONCLUSIONS: Inflammatory bowel disease patients on TNF inhibitors frequently reported musculoskeletal manifestations. Increased recognition of SpA occurred with use of an SpA self-reported questionnaire in IBD patients: this could alter management and improve patient outcomes. Clinical drug-induced lupus erythematosus was uncommon.

Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat.

Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18-20 (0.5 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P = 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol.

Early predictors of colectomy and long-term maintenance of remission in ulcerative colitis patients treated using anti-tumour necrosis factor therapy.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are used as induction and maintenance therapy in ulcerative colitis (UC) refractory to standard therapy and as rescue therapy in acute severe UC (ASUC). AIMS: To determine long-term outcomes including colectomy rates, predictors of maintenance of response and remission, risk of serious adverse events by reviewing 12-year clinical experience from a single centre in Australia. METHODS: Seventy-one patients with moderate-severe UC (Mayo score ≥6) (n = 52) and ASUC (n = 19) treated with anti-TNF agents were included. Primary end-points were colectomy at 12 weeks and colectomy-free survival at last follow up. Secondary endpoints included clinical response (decrease in Mayo score of ≥3) and remission (Mayo score ≤2). RESULTS: Colectomy at 12 weeks was 1%, and colectomy-free survival was 69%. Using full Mayo score, at 3 months, 32/37 (87%) refractory and 9/12 (75%) ASUC patients responded to anti-TNF therapy; 19/37 (51%) refractory and 8/12 (67%) ASUC patients were in remission. Long-term response rates (mean follow up 37.4 months) were 24/44 (55%) and 11/15 (73%) in refractory and ASUC groups respectively. Long-term remission rates were 43% in refractory and 60% in ASUC patients. Twenty two of 71 (31%) underwent colectomy (mean time 50.4 months). Clinical non-response at 3 months was a predictor of colectomy (hazard ratio = 9.346; P = 0.001). ASUC predicted long-term maintenance of response (odds ratio 19.4; P = 0.013) and remission (odds ratio 6.13; P = 0.037). Two of 71 patients had serious infections. CONCLUSIONS: Anti-TNF therapy is effective in both refractory and ASUC. We argue that early anti-TNF therapy may improve outcome in UC.

The Menstrual Disorder of Teenagers (MDOT) Study No. 2: Period ImPact and Pain Assessment (PIPPA) Tool Validation in a Large Population-Based Cross-Sectional Study of Australian Teenagers.

STUDY OBJECTIVE: To validate the Period ImPact and Pain Assessment (PIPPA) self-screening tool for menstrual disturbance in teenagers. DESIGN: Cross-sectional study. SETTING: Three senior high schools in the Australian Capital Territory (ACT), Australia. PARTICIPANTS: A total of 1066 girls between 15 and 19 years of age. INTERVENTIONS AND MAIN OUTCOME MEASURES: A quantitative paper survey collected self-reports of menstrual bleeding patterns, typical and atypical symptoms, morbidities, and interference with daily activities. Multiple correspondence analysis was used to examine associations between PIPPA questions. Generalized linear models compared total score and subscores by validation criteria: pain, school absence, and body mass index (BMI). Receiver operating characteristic curves were used to evaluate the predictiveness of menstrual disturbance indicators by total PIPPA score. RESULTS: Reports of pain, interference, and concern within the PIPPA items and between both the MDOT and PIPPA questionnaires were significantly correlated (P < .0001). The indicator "missing school" was highly associated (P < .0001) with pain and interference. Obesity (BMI ≥30) was associated with higher PIPPA scores, as was underweight (BMI≤18.4). Where 0 = no disturbance, 5 = high disturbance, aggregated PIPPA scores found 75% scoring 0-2 (out of 5) and 25% scoring 3-5 (257/1037). High scores of 4 or 5 (out of 5) were 7% (72/1037) and 3.7% (38/1037), respectively. CONCLUSION: PIPPA is a valid screening tool for pain-related menstrual disturbance that affects functioning in young women. PIPPA subdomains of pain/interference have good validity relative to indicators of pain and interference and are responsive to age, BMI, and school absence differences.

Clinical role of flow cytometry in redefining bone marrow involvement in diffuse large B-cell lymphoma (DLBCL) - a new perspective.

AIMS: The clinical role of flow cytometry in staging bone marrow in diffuse large B-cell lymphoma (DLBCL), especially its impact on outcome, remains uncertain. The aim was to determine the contribution of flow cytometry to conventional staging, and to study the impact of this revised staging on survival. METHODS AND RESULTS: One hundred and thirteen cases of DLBCL diagnosed at The Canberra Hospital from 1996 to 2005 were identified. Blinded analysis of bone marrow (BM) morphology and flow cytometric data showed involvement on morphology (M) in 25 (22.1%) cases, on flow cytometry (F) in 21 (18.6%) cases and overall (M + F) in 32 cases (28.3%); discordance was noted in 16 cases (16.1%). Cases with and without marrow involvement on conventional staging alone (M) had no significant difference in survival (P = NS). However, when BM involvement was defined as positivity on morphology and/or flow cytometry (M + F), the median survival of patients with involvement was significantly worse than patients without involvement (P = 0.026). CONCLUSIONS: Flow cytometry-positive cases should be included with those positive on morphology in a summative model to define BM involvement in DLBCL, as it may have a potential impact on predicting outcome.

Infliximab in severe active ankylosing spondylitis with spinal ankylosis.

BACKGROUND: Infliximab is an anti-tumour necrosis factor monoclonal antibody, which significantly improves pain, stiffness and functional disability outcomes in patients with active ankylosing spondylitis. There are limited data available on the efficacy of this treatment for the subgroup with established spinal ankylosis. AIM: To compare the treatment response of infliximab in active severe ankylosing spondylitis for patients with and without radiographic evidence of spinal ankylosis in the clinical practice setting. METHODS: Twenty-seven patients with mean Bath Ankylosing Spondylitis Disease Activity Index of 8.7, all HLA-B27 positive, with 11 (41%) having spinal ankylosis, were studied for 54 weeks. The qualification for initial and ongoing infliximab treatment was defined by the Australian Pharmaceutical Benefit Schedule (PBS), and 5 mg/kg of infliximab was given at 0 week (baseline), repeated at 2 and 6 weeks and every 6 weeks thereafter. At each time point, PBS-mandated and international consensus response measures were completed. Disease activity and outcome measures for spinal ankylosis subgroup and those who did not have spinal ankylosis were cross-sectionally compared at baseline and 1 year. RESULTS: Patients with spinal ankylosis tended to be older (P = 0.01). Although the subgroup with spinal ankylosis had higher baseline activity scores, the only significant difference between the subgroups was the degree of morning stiffness (P = 0.04). By 54 weeks, all patients including the subgroup with spinal ankylosis fulfilled the PBS criteria for continuation of treatment. Majority of patients including the subgroup with spinal ankylosis achieved the various international consensus response measures. Patients with spinal ankylosis also experienced significant improvements in health-related quality of life, with majority returning to full-time employment by 1 year. CONCLUSION: In real-life clinical practice, patients with established disease with spinal ankylosis and high levels of inflammation and disease activity can achieve a major clinical response with infliximab.

Quality of life after infection in total joint replacement.

PURPOSE: To compare the health-related quality of life and functional outcomes of patients with and without periprosthetic infection after total joint replacement (TJR). METHODS: 62 uncomplicated TJRs and 34 TJRs complicated with deep infection were compared using a visual analogue scale for satisfaction, the Western Ontario and McMaster Universities Osteoarthritis Index, Assessment of Quality of Life, and Short Form-36. RESULTS: Patients with complicated TJR had significantly poorer satisfaction in outcome (p<0.0001) and disease-specific functional outcomes (p<0.0001). Six of the 8 health-related quality-of-life scores were also significantly poorer (p<0.05). These results persisted after controlling for age, sex, and follow-up period in a multiple regression analysis. CONCLUSION: Infection following TJR reduces patient satisfaction and seriously impairs functional health status and health-related quality of life. When hospitals are balancing the costs of preventative measures with the costs of treating infection in TJR, the effect on patients' quality of life must be considered. Our findings argue strongly for allocation of health care resources to minimise the occurrence of infection after TJR.

Referral patterns of general dental practitioners for bone grafting and implant placement.

BACKGROUND: Dental implant rehabilitation is a well-established procedure often conducted in the general dental practise setting. The outcomes for implant placement are reliable when the recipient site is favourable. The goal of this study was to assess the accuracy with which general dental practitioners (GDP) assess the bone volume available for implant placement and their referral patterns for implant sites, which may require bone grafting. METHODS: Fifty-three GDP were surveyed and asked to assess five different scenarios and cone-beam scans for difficulty (0, 'no difficulty'; 5, 'the most difficult'), and bone grafting requirements ('yes'/'no' and 'who to perform'), prior to implant placement. RESULTS: The GDP assessment of difficulty for the cases was: no graft required, 1.88; aesthetic zone involvement, 3.25; vertical deficiency, 2.8; sinus lift required, 3.68; and horizontal deficiency, 4.4. GDP seemed to have some difficulty identifying which cases required a bone graft, occasionally grafting a site with sufficient bone (12.5%), or not grafting a site with insufficient bone (45-75%). CONCLUSIONS: These results show that GDP are accurate in assessing the difficulty of an implant case and conservative when it comes to attempting these complex cases. GDP are less confident when it comes to recognizing cases that require bone grafting, and what options are available.

Etanercept in severe active rheumatoid arthritis: first Australian experience.

BACKGROUND: Etanercept reduces disease activity in adults with chronic rheumatoid arthritis (RA) who are resistant to other therapies. Medicare Australia Pharmaceutical Benefit Scheme subsidized treatment (since August 2003) restricts etanercept availability to a most drug-resistant RA population. The aim of the study was to assess the efficacy of etanercept in this unique group after 12 months of therapy. METHODS: A prospective study of the first 50 consecutive private practice, adult RA patients whom were commenced on etanercept. The primary efficacy measures included short form 36 scores, Disease Activity Score 28, American College of Rheumatology (ACR) response improvement in per cent and the ACR individual core set components at baseline, 3 and 12 months. Analysis was by intention to treat. RESULTS: There was significant improvement in all mean short form 36 component scores (P < 0.05) and all ACR core set component scores (P < 0.05) comparing 12 months to baseline. The disease activity score 28 also significantly fell from baseline at both 3 and 12 months (P < 0.05). The ACR 20% response significantly improved (P < 0.05) both at baseline to 3 months 92% (81.2, 96.9) and to 12 months 80% (67.0, 88.8). Serious adverse events occurred in 16%. At 12 months 88% completed treatment. CONCLUSION: Etanercept therapy will, by 3 and 12 months, significantly improve the short form 36, disease activity score 28, ACR 20% response and core set components. Our results are similar to international studies using etanercept in efficacy and tolerance despite our cohort being more resistant to preceding drug therapy. Etanercept offers this unique active severe refractory late RA Australian population a new therapeutic option to control their disease.

The association of scapho-trapezio-trapezoid osteoarthrosis and scapholunate dissociation.

There are two parts to this paper. In the first part we report 18 cases of bilateral scapho-trapezio-trapezoid osteoarthrosis associated with uni- or bilateral scapholunate dissociation. This case series was followed prospectively using repeat clinical assessments and radiographs. We were able to document the progression of both the clinical manifestations and radiographic features of the scapholunate dissociation in these patients. In the second part of the paper we compared the radiographic indices of scapholunate dissociation seen in our series, that is, the scapholunate angle and interval, with those of a control group over time, to determine if there was a significant difference. The control group differed from our series principally by being devoid of any clinical or radiographic evidence of scapho-trapezio-trapezoid osteoarthrosis. We found that our case series already had some radiographic evidence of scapholunate attrition at presentation and that at follow-up the scapholunate dissociation became more pronounced both clinically and radiographically relative to the controls. The authors propose a theory to explain the association and temporal relationship between the two conditions.

Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease.

BACKGROUND: Muscle wasting or sarcopenia arising from chronic inflammation is found in 60% of patients with Crohn's disease. Transcriptional protein NF-κB reduces muscle formation through MyoD transcription and increases muscle breakdown by proteolysis. AIM: As TNF is a potent activator of NF-κB, and anti-TNF agent infliximab (IFX) prevents NF-κB activation, to determine whether or not Crohn's patients treated with IFX gain muscle volume and strength. METHODS: We performed a prospective, repeated-measures cohort study in adult Crohn's disease patients with an acute disease flare. Patients were instructed not to vary diet or activity. Concomitant medications were kept stable. At week 1 (pre-treatment), week 16 (post-IFX induction) and week 25 (post-first IFX maintenance dose), we assessed (i) MRI volume of quadriceps femoris at anatomical mid-thigh; (ii) maximal concentric quadriceps contractions strength at three specific speeds of contraction; (iii) physical activity by validated instrument (IPAQ); (iv) Three-day food record of intake and composition (food-weighing method); (v) Serum levels of IL6. RESULTS: Nineteen patients (58% female; mean age 33.2 ± 10.7 years) were recruited. IFX increased muscle volume in both legs from baseline (right, 1505 cm(3) ) to week 25 (right, 1569 cm(3) ; P = 0.010). IFX also increased muscle strength in both legs from baseline (right 30°/s, 184.8 Nm) to week 25 (right 30°/s, 213.6 Nm; P = 0.002). Muscle volume gain correlated with male gender (P = 0.003). Significant gains in muscle volume and strength were unrelated to prednisolone use. Serum IL6 levels decreased by week 25 (P = 0.037). CONCLUSION: The anti-TNF agent infliximab reverses inflammatory sarcopenia in patients with Crohn's disease.

Assessing health-related quality of life following myocardial infarction: is the SF-12 useful?

We report on the responsiveness of the SF-12 to changes in quality of life following acute myocardial infarction. Scores at 1, 6, 12, and 24 weeks postdischarge were compared with pre-MI health. Statistically significant differences and standardized response means were examined. Results were compared with the SF-36 subscales and previous reports. Respondents (n = 65) reported the expected poorer physical health at every follow-up, while expected changes in emotional health were observed at 6 but not 24 weeks. Comparison with the SF-36 subscales showed that although the SF-12 reflected the expected pattern of physical health, the summary score obscured an important association between perceptions of general health and participation in usual activities. This information is relevant for developing and evaluating rehabilitation interventions and self-managed recovery following MI. The SF-12 scores obscure important distinctions between quality of life domains, and are therefore not recommended for use following acute MI.

Health consequences of social-role careers for women: a life-course perspective.

This study aimed to demonstrate the importance of early adulthood social-role participation in determining the health of women over the life course. It used Australian Family Project data from a nationally representative proportional stratified sample of 1-in-1000 women aged between 20 and 59 years in 1986-87 (n = 1678); and data from a follow-up survey conducted in 1990 using project participants who were living in Sydney at the time of the baseline (n = 291). Social-role participation was measured over each participant's life using retrospective histories of employment, marital status and parental status. Validity and reliability tests supported the use of these histories. Health was measured by retrospective accounts of serious chronic disease onset and indicators of self-rated health. After considering a broad range of confounders, early adulthood social-role careers were found to vary significantly in their risk of serious chronic disease and levels of self-rated health. These findings suggest that the influence of society's social structures on health for women goes beyond causes related to conventional socioeconomic differentials or arbitrary periods of social-role participation. The nature of the associations are complex and dynamic, involving both the mixture and timing of social events and transitions. This conclusion supports a life-course approach in which social careers are perceived as cumulative, providing women with lessons, liabilities and resources that influence the way they age and meet the realities of life.

Hospital outcomes management: the Care Continuum and Health Outcomes Project.

The Care Continuum and Health Outcomes Project is part of a national initiative to build an outcomes management approach in health care. This paper examines the baseline performance of the study. In 1995-96, 7154 Australian Capital Territory hospital inpatients were selected to take part in a five-wave survey over six months. In addition to the survey, the project involved the unit record linkage of routine data collections. A total of 5668 people (79%) agreed to participate in the survey, with 85% of these people agreeing to release their Medicare data. There were significant variations in participation rates between hospitals and wards. Factors contributing to these variations included patient socioeconomic status, disease type and illness severity. In conclusion, the success in establishing the project indicates that it is possible to conduct a broad scientific study within the health system, and that there are strong implications that ongoing scientific evaluations can be embedded within routine clinical practice.

Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial.

BACKGROUND: Controversy exists whether different continuous positive airway pressure (CPAP) weaning methods influence time to wean off CPAP, CPAP duration, oxygen duration, Bronchopulmonary Dysplasia (BPD) or length of admission. AIMS: In a multicentre randomised controlled trial, the authors have primarily compared CPAP weaning methods impact on time to wean off CPAP and CPAP duration and secondarily their effect on oxygen duration, BPD and time of admission. METHODS: Between April 2006 and October 2009, 177 infants <30 weeks gestational age (GA) who fulfilled stability criteria on CPAP were randomised to one of the three CPAP weaning methods (M). M1: Taken 'OFF' CPAP with the view to stay 'OFF'. M2: Cycled on and off CPAP with incremental time 'OFF'. M3: As with m(2), cycled on and off CPAP but during 'OFF' periods were supported by 2 mm nasal cannula at a flow of 0.5 l/min. RESULTS: Based on intention to treat analysis, there was no significant difference in mean GA or birthweight between the groups (27.1 ± 1.4, 26.9 ± 1.6 and 27.3 ± 1.5 (weeks ± 1SD) and 988 ± 247, 987 ± 249 and 1015 ± 257 (grams ± 1SD), respectively). Primary outcomes showed M1 produced a significantly shorter time to wean from CPAP (11.3 ± 0.8, 16.8 ± 1.0, 19.4 ± 1.3 (days ± 1SE) p<0.0001, respectively) and CPAP duration (24.4 ± 0.1, 38.6 ± 0.1, 30.5 ± 0.1 (days ± 1SE) p<0.0001, respectively). All the secondary outcomes were significantly shorter with M1, (oxygen duration: 24.1 ± 1.5, 45.8 ± 2.2, 34.1 ± 2.0 (days ± 1SE) p<0.0001, BPD: 7/56 (12.5%), 29/69 (42%), 10/52 (19%) p=0.011 and length of admission: 58.5 ± 0.1, 73.8 ± 0.1 69.5 ± 0.1 (days ± 1SE) p<0.0001, respectively). CONCLUSION: Method 1 significantly shortens CPAP weaning time, CPAP duration, oxygen duration, BPD and admission time.

The prognostic significance of single hormone receptor positive metastatic breast cancer: an analysis of three randomised phase III trials of aromatase inhibitors.

We analysed the outcomes of women with metastatic breast cancer (MBC) from three randomised phase III trials of aromatase inhibitors according to oestrogen receptor (ER) and progesterone receptor (PgR) status. Both receptors were analysed in 1010 of the 1870 women (54%), including 31 that were ER-/PgR-, which were excluded. Of the remaining 979, 726 (74%) were ER+/PgR+ but 253 were single hormone receptor positive (213 ER+/PgR-, 40 ER-/PgR+). Although there were no differences in clinical benefit or time to progression, the median overall survival of women with ER+/PgR+ tumours was significantly longer than those with single HR positive tumours (800 versus 600 days, p=0.01). In women with ER+ tumours, the median overall survival of those with tumours that were also PgR+ was significantly longer than those that were PgR- (800 versus 625 days, p=0.02). The PgR status is an important prognostic factor for survival in MBC.

Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and oesophageal cancer in Barrett's oesophagus.

BACKGROUND: It has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high-risk group for Barrett's oesophagus. AIM: To determine whether proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus influences markers for risk development of subsequent high-grade dysplasia/adenocarcinoma. METHODS: A review of all patients with Barrett's oesophagus entering a surveillance programme was undertaken. Five hundred and two patients diagnosed with Barrett's oesophagus were assessed on diagnosis for endoscopic macroscopic markers or low-grade dysplasia. Subsequent development of high-grade dysplasia/adenocarcinoma was documented. The relationship between the initiation of proton pump inhibitor therapy prior to the diagnosis of BE and the presence of macroscopic markers or low-grade dysplasia at entry was determined. RESULTS: Fourteen patients developed high-grade dysplasia/adenocarcinoma during surveillance. Patients who entered without prior proton pump inhibitor therapy were 3.4 times (95% CI: 1.98-5.85) more likely to have a macroscopic marker or low-grade dysplasia than those patients already on a proton pump inhibitor. CONCLUSIONS: Use of proton pump inhibitor therapy prior to diagnosis of Barrett's oesophagus significantly reduced the presence of markers used to stratify patient risk. Widespread use of proton pump inhibitors will confound surveillance strategies for patients with Barrett's oesophagus based on entry characteristics but is justified because of the lower risk of neoplastic progression.

A comparative study of the quality of DNA obtained from fresh frozen and formalin-fixed decalcified paraffin-embedded bone marrow trephine biopsy specimens using two different methods.

BACKGROUND: Given its prognostic value, there is renewed interest in molecular staging in non-Hodgkin's lymphoma (NHL) using immunoglobulin heavy and light chain (IgH, IgL) gene rearrangements. AIMS: To compare the efficiency of DNA amplification from fresh frozen and formalin-fixed decalcified paraffin-embedded (FFDPE) bone marrow trephines for use in molecular staging using two methods. METHODS: After manually extracting DNA from 13 FFDPE and 14 fresh frozen trephine biopsy specimens, two methods were used to test for amplifiability: use of the amplification control master mix supplied in the In Vivo Scribe immunoglobulin heavy chain (IgH) clonality kit, which creates 5 amplicons between 96-600 base pairs (bp); and real-time amplification of the beta-globin gene. RESULTS: Using the first method, the mean maximum length of amplicons generated from FFDPE trephines was statistically lower at 300 bp compared to fresh frozen samples, all of which generated amplicons up to 600 bp in size (p<0.001). Real-time amplification of the beta-globin gene showed that the mean crossing threshold of fresh frozen samples was statistically lower than that of FFDPE samples (23.48 (95% CI 22.47 to 24.48) vs 33.64 (95% CI 32.15 to 35.12); p<0.001). CONCLUSIONS: Although amplifiable DNA can be extracted from both fresh-frozen and FFDPE trephine samples for IgH/IgL analysis, freshly frozen specimens are superior as a source of template DNA, especially for higher base pair PCR products.