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.

Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death.

Autoimmune hepatitis in a demographically isolated area of Australia.

BACKGROUND: Previous studies describing autoimmune hepatitis (AIH) come from liver transplant centres in which a skewed distribution of cases may give a misleading picture of the incidence of AIH and its natural history. This series describes AIH in a stable and demographically discrete population of patients in the Australian Capital Territory (ACT) and the surrounding region. METHODS: In 42 patients with type 1 AIH (point prevalence 8 per 100,000 population), clinical, laboratory and histological features at presentation, response to initial therapy, details of maintenance therapy and outcome were recorded. RESULTS: Consistent with other publications, the male-to-female ratio was 1:3, mean age at presentation was 53 years and 24% had cirrhosis at diagnosis. Most patients (86%) responded to initial therapy and 67% went into long-term remission. One patient died from liver failure and none required liver transplantation. Azathioprine was included in the treatment regimen in 74% of cases with doses generally <2 mg/kg. Azathioprine dose greater than or equal to 2 mg/kg was associated with better clinical outcome, but this did not reach statistical significance. A higher proportion of female patients had cirrhosis at presentation (9/10 vs 1/10; P= 0.24). CONCLUSION: In this Australian community-based study, type 1 AIH was primarily a disease of later life, responded to conventional immunosuppressive therapy and generally has a good prognosis. Further study of the use of azathioprine is warranted to determine the optimal dose.

A randomised, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFE-II Study).

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) often coexist. The aim was to investigate whether restoring sinus rhythm (SR) could improve cardiac function, symptoms, exercise capacity and quality of life (QoL) in patients with chronic heart failure. METHODS: Patients with HF and persistent AF receiving guideline-recommended treatments, including anticoagulants, were eligible for the study. Patients were randomised to either rhythm (treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored) or rate control. Anticoagulants were continued throughout the study regardless of rhythm, unless contraindications developed. Both groups were treated with beta blockers and/or digoxin to reduce the heart rate to <80 bpm at rest and <110 bpm after walking. Symptoms, walk distance (6-minute corridor walk test, 6MWT), QoL and cardiac function were assessed at baseline and 1 year. RESULTS: 61 patients with HF and persistent AF (median duration 14 months (IQR 5 to 32)) were randomly assigned to a rate or rhythm control strategy. Of patients assigned to rhythm control (n = 30), 66% were in SR at 1 year, and 90% of those assigned to rate control (n = 31) achieved the heart rate target. At 1 year, NYHA class (p = 0.424) and 6MWT distance (p = 0.342) were similar between groups but patients assigned to rhythm control had improved LV function (p = 0.014), NT-proBNP concentration (p = 0.046) and QoL (p = 0.019) compared with those assigned to rate control. Greatest improvement was seen in patients in whom SR was maintained. CONCLUSION: Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control.

A brief cognitive behavioural preimplantation and rehabilitation programme for patients receiving an implantable cardioverter-defibrillator improves physical health and reduces psychological morbidity and unplanned readmissions.

OBJECTIVE: To assess the clinical and cost effectiveness of a brief home-based cognitive behavioural rehabilitation programme (the ICD Plan) for patients undergoing implantation of a cardiac defibrillator. DESIGN: A prospective multicentred, intention-to-treat, cluster-randomised controlled trial. SETTING: Eight implantable cardioverter-defibrillator (ICD) implantation centres in the UK. PATIENTS: Consecutive series of patients undergoing implantation with an ICD. INTERVENTIONS: The control group received usual care and advice from an experienced healthcare professional. The intervention group received usual care plus the ICD Plan. The plan was introduced before implantation, with three further brief telephone contacts with the nurse over the next 12 weeks. MAIN OUTCOME MEASURES: Health-related quality of life (Short Form Health Survey (SF-12)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), activity limitations (subscale from the Seattle Angina Questionnaire (SAQ)), unplanned admissions and other economic data using a questionnaire developed for the study. RESULTS: 192 patients were recruited to the study (71 intervention, 121 control). At 6 months after surgery the intervention group had better physical health (37.83 vs 34.24; p<0.01), fewer limitations in physical activity (34.02 vs 31.72; p = 0.04), a greater reduction in the proportion of patients with a borderline diagnosis of anxiety (21% vs 13%; p = 0.60) and depression (13% vs 2%; p = 0.30), more planned ECGs (89% vs 66%; p = 0.04) and 50% fewer unplanned admissions (11% vs 22%; p<0.01). CONCLUSIONS: The ICD Plan improved health-related quality of life, reduced the incidence of clinically significant psychological distress and significantly reduced unplanned readmissions. It is a cost effective and easily implemented method for delivering rehabilitation and psychological care to patients undergoing ICD implantation. TRIAL REGISTRATION NUMBER: ISRCTN70212111.

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.

Development of a measure of the concerns held by people with implanted cardioverter defibrillators: the ICDC.

OBJECTIVES: To develop a questionnaire to measure the extent and severity of the concerns of people with an implanted cardioverter defibrillator. DESIGN: Items were generated from patient interviews, expert review and the research literature on patients' worries and concerns. A pilot version was administered to a series of ICD patients and repeated for test-retest reliability 6 weeks later. Psychometric tests including the screen test, factor analysis and various reliability assessments were undertaken. It was predicted that the greater the extent and severity of concerns, the greater the anxiety experienced by the ICD patient. Scores were compared with a validated measure of anxiety and depression administered at the same time. RESULTS: Fifty-seven (64%) patients completed and returned the questionnaire and a further 22 (100% of those asked) completed the 6-week retest. Reliability and validity appeared to be good and two factors were identified. Both total score and the individual factor scores correlated moderately with anxiety. CONCLUSIONS: The questionnaire appears to reflect patients' concerns and, as predicted, these were associated with the patients' anxiety level. The scale requires further testing to reveal if it is of use both clinically and for research purposes.

Giant right coronary artery aneurysm presenting as a mediastinal mass.

Coronary artery aneurysms are commonly of atherosclerotic origin and are frequently asymptomatic. However, they may have varied presentations including angina, myocardial infarction, and sudden death. A case of a giant right coronary artery aneurysm presenting with acute myocardial infarction is presented, where the aneurysm appeared to be a mediastinal mass on transthoracic and transoesophageal echocardiography. Although computed tomography and magnetic resonance imaging of the heart suggested the correct diagnosis, definitive proof came from coronary angiography. Coronary artery aneurysms should be considered in the differential diagnosis of mediastinal masses.

Cognitive-behavioural rehabilitation programme for patients with an implanted cardioverter defibrillator: a pilot study.

OBJECTIVES: The effectiveness of a comprehensive 12-week CR programme for ICD patients was evaluated. DESIGN: All surviving and suitable ICD patients being cared for by a regional implantation centre were invited to attend a 12-week cognitive-behavioural cardiac rehabilitation programme that had been modified to meet the needs of this group. Patients assenting were randomized to either an immediate treatment or a waiting treatment group. Measures were taken prior to randomization, at the end of the treatment or waiting period, at the end of the second treatment group for that group only and at three months post-treatment for both groups. OUTCOME MEASURES: The Hospital Anxiety and Depression Scale, the Total Concerns Questionnaire, the Quality of Life after Myocardial Infarction Questionnaire, the EuroQual (subjective health rating scale), the Shuttle Test and a number of ICD shocks and ATP episodes were used in this study. RESULTS: For those patients willing and able to attend, the cognitive-behavioural CR programme produced significant benefits in terms of psychological and functional adaptation to living with the device. CONCLUSIONS: A comprehensive 12-week CR programme that incorporated both psychological and exercise-based components significantly reduced anxiety and depression and improved quality of life of ICD patients. It is not clear if these benefits are sustained.

Successful use of oral linezolid as a single active agent in endocarditis unresponsive to conventional antibiotic therapy.

Treatment of resistant gram-positive endocarditis is difficult. We report a case of resistant Staphylococcus epidermidis endocarditis that failed to respond to conventional antibiotic therapy but was treated successfully with an oral regimen of a new antibiotic, linezolid as a single active agent. This case report demonstrates the use of linezolid as an effective alternative to conventional antibiotics in such cases.

Ongoing trials of cardiac resynchronisation.

Heart failure is an increasingly common and debilitating condition for which pharmacological therapy has, so far, provided only partial relief. Despite medical therapy the overall prognosis remains poor with high rates of sudden death and death from progressive heart failure. Device based therapies offer considerable promise both for the relief of symptoms and for improving prognosis. Cardiac resynchronisation therapy (CRT) has already been shown to improve the symptoms of heart failure when optimal pharmacological therapy (including aggressive diuretic therapy, ACE inhibitors, b-blockers and spironolactone) has failed. Two large trials (CARE-HF and COMPANION) are currently investigating the effects of CRT on morbidity and mortality in patients with heart failure and sinus rhythm who have left ventricular systolic dysfunction and ventricular dyssynchrony. A series of small and medium sized studies are assessing the effects of CRT in patients similar to the above but who also have atrial fibrillation. Other potential indications for CRT that are being explored include heart failure due to left ventricular diastolic function and for the prevention of iatrogenic dyssynchrony caused by conventional pacing. The MADIT-II study suggests a small benefit from routine implantation of defibrillators in patients with heart failure who have a markedly depressed (<30%) ejection fraction due to prior myocardial infarction even in the absence of specific marker of risk for sudden arrhythmic death. Much greater benefit was observed in patients with QRS >150 msec, an ECG marker for cardiac dyssynchrony. The COMPANION trial will not only assess the effects of CRT alone but also the effects of a combined CRT and defibrillator device. Premature over-interpretation of the limited amount of existing data threatens to undermine the evidence that will form the basis of future guidelines and funding decisions. Those involved in trials have an ethical duty to minimise device implantation into patients who have been randomised to the control group (cross-overs). Doctors may have difficulty explaining to patients why they implanted a CRT device should the current trials not show benefit. Patients should be warned that CRT is still an experimental therapy that has not yet been proven to alter outcome substantially.

An unusual case of infective endocarditis.

A rare case of Corynebacterium striatum endocarditis on a bioprosthetic aortic valve replacement, treated medically, is reported. The presentation was subacute, and initially endocarditis screening was negative. Because of the failure of symptoms to settle further screening was performed which confirmed the organism in several sets of blood cultures. This emphasises the importance of persistent screening for endocarditis if the history raises any suspicion of this potentially serious infection, especially in the presence of prosthetic valves.

Clinical usefulness of microbiological diagnostic tools in the management of periodontal disease.

Periodontal diseases comprises a group of chronic inflammatory conditions affecting tooth supporting structures. It has been known for a long time that pathogenic oral bacteria colonizing the tooth surface are associated with the initiation of the disease process. However, to date, a dozen or so bacterial species have been implicated in the pathogenesis of periodontal disease and no one species by itself is synonymous with disease onset. This multibacterial etiology renders the diagnosis of active periodontal disease based on microbiological data difficult. Numerous studies have attempted to relate the usefulness of microbiological diagnostic aids such as microscopy, bacterial culture, immunological and enzymatic assays. Furthermore, recent technical advances have resulted in the use of nucleic acid probes and amplification techniques for the identification of genetic material belonging to potential periodontal pathogens. Despite the availability of a large number of microbiological testing protocols, identification of the microbial etiological agents remains hampered by the complexity of the microbial challenge during periodontal disease. This review discusses the clinical usefulness of these tests in detection and management of periodontal disease.

Hyperkalemia diagnosed by implantable cardioverter defibrillator T wave sensing.

A patient with congestive heart failure and an ICD had undergone atrioventricular nodal ablation and optimization of heart failure medical therapy. Intracardiac T wave sensing by the ICD drew attention to the new development of asymptomatic hyperkalemia. Surface ECG features of hyperkalemia were not readily identified due to pacemaker dependence.

Clinical use of intracardiac impedance: current applications and future perspectives.

For over 40 years the measurement of intracardiac impedance has been proposed as a method of assessing the contractile state of the heart muscle. This technique requires the positioning of one or more intracavitary electrodes and the generation of an electric field from an alternating current source. Variations in the calculated impedance signal reflect changes in the ventricular blood pool volume adjacent to the electrodes. Intracardiac impedance measurement has been successfully developed as a research tool to assess myocardial contractility, and from this, clinical uses have evolved. Commercial rate responsive pacing systems use intracardiac impedance to assess the inotropic state of the heart. Further development of this technology might allow hemodynamic discrimination of cardiac arrhythmias.