Clinical applications of high-intensity focused ultrasound.

Ultrasound has been developed for therapeutic use in addition to its diagnostic ability. The use of focused ultrasound energy can offer a non-invasive method for tissue ablation, and can therefore be used to treat various solid tumours. High-intensity focused ultrasound is being increasingly used in the treatment of both primary and metastatic tumours as these can be precisely located for ablation. It has been shown to be particularly useful in the treatment of uterine fibroids, and various solid tumours including those of the pancreas and liver. High-intensity focused ultrasound is a valid treatment option for liver tumours in patients with significant medical co-morbidity who are at high risk for surgery or who have relatively poor liver function that may preclude hepatectomy. It has also been used as a form of bridging therapy while patients awaiting cadaveric donor liver transplantation. In this article, we outline the principles of high-intensity focused ultrasound and its clinical applications, including the management protocol development in the treatment of hepatocellular carcinoma in Hong Kong by performing a search on MEDLINE (OVID), EMBASE, and PubMed. The search of these databases ranged from the date of their establishment until December 2015. The search terms used were: high-intensity focused ultrasound, ultrasound, magnetic resonance imaging, liver tumour, hepatocellular carcinoma, pancreas, renal cell carcinoma, prostate cancer, breast cancer, fibroids, bone tumour, atrial fibrillation, glaucoma, Parkinson's disease, essential tremor, and neuropathic pain.

Self-management support and other alternatives to reduce the burden of asthma and chronic obstructive pulmonary disease.

While pharmacotherapy is important in the management of asthma and chronic obstructive pulmonary disease, it is also important to consider additional interventions that can further reduce the burden of ill health for patients, their families and the health care system. In this review, the evidence in favour of self-management support that leads to successful self-care by the patient is reviewed, and the key components of successful strategies are outlined; areas where more research is needed are identified. In addition to self-management support, other methods of delivering care, such as telemonitoring, admission avoidance, assisted discharge schemes and use of lay educators, are reviewed.

Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study.

We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.

Lung perfusion and chest wall configuration is altered by glossopharyngeal breathing.

Glossopharyngeal insufflation is used by competitive breath-hold divers to increase lung gas content above baseline total lung capacity (TLC) in order improve performance. Whilst glossopharyngeal insufflation is known to induce hypotension and tachycardia, little is known about the effects on the pulmonary circulation and structural integrity of the thorax. Six male breath-hold divers were studied. Exhaled lung volumes were measured before and after glossopharyngeal insufflation. On two study days, subjects were studied in the supine position at baseline TLC and after maximal glossopharyngeal insufflation above TLC. Tc 99(m) labelled macro-aggregated albumin was injected and a computed tomography (CT) scan of the thorax was performed during breath-hold. Single photon emission CT images determined flow and regional deposition. Registered CT images determined change in the volume of the thorax. CT and perfusion comparisons were possible in four subjects. Lung perfusion was markedly diminished in areas of expanded lung. 69% of the increase in expired lung volume was via thoracic expansion with a caudal displacement of the diaphragm. One subject who was not proficient at glossopharyngeal insufflation had no change in CT appearance or lung perfusion. We have demonstrated areas of hyperexpanded, under perfused lung created by glossopharyngeal insufflation above TLC.

Outcome of patients receiving high dose vasopressor therapy: a retrospective cohort study.

The aim of this study was to determine the hospital survival of patients receiving high doses of catecholamines. A retrospective observational study was conducted in a 22-bed multidisciplinary adult intensive care unit of a tertiary referral university hospital. All patients (n = 64) receiving > 100 microg/min of adrenaline or noradrenaline or adrenaline and noradrenaline combined over a one-year period were studied to determine survival to intensive care unit and hospital discharge. Four patients survived to intensive care unit discharge and hospital discharge (6.25%, 95% CI 0.3 to 12.2%). Survival was 3.3% (95% CI 0 to 7.9%) in the subgroup of 60 patients who received > 100 microg/min noradrenaline and 3.6% (95% CI 0 to 8.6%) in the 55 patients who received > 2 microg/kg/min noradrenaline. None of the 32 patients who received > 200 microg/min noradrenaline survived. We conclude that the survival of patients requiring high doses of catecholamines is poor but the use of such doses is probably not futile. It remains for individual clinicians, patients and their surrogates to decide whether use of high doses of vasopressor is appropriate, given the low probability of survival.

Double blind randomised controlled trial of two different breathing techniques in the management of asthma.

BACKGROUND: Previous studies have shown that breathing techniques reduce short acting beta(2) agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. METHODS: After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. RESULTS: Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. CONCLUSION: Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises.

Accuracy of central venous pressure monitoring during simultaneous continuous infusion through the same catheter.

Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.

An unusual complication of interscalene brachial plexus catheterization: delayed catheter migration.

This case report describes the delayed migration of an interscalene brachial plexus catheter that was inserted for postoperative analgesia and to facilitate physiotherapy after shoulder surgery. Approximately 18 h after surgery the catheter was found to have migrated into the interpleural space, which could have resulted in a serious complication, namely a pneumothorax.

Traditional and patient-centred outcomes with three classes of asthma medication.

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.

When can personal best peak flow be determined for asthma action plans?

BACKGROUND: Written asthma action plans based on personal best peak expiratory flow (PEF) consistently improve health outcomes, whereas those based on predicted PEF do not. Guidelines state that personal best PEF should be assessed over 2-3 weeks during good asthma control, but it is unclear how long to wait after commencing or changing treatment. METHODS: Electronically recorded spirometric data from 61 subjects with initially poorly controlled asthma from a 72 week budesonide study were analysed. For each week, average morning pre-bronchodilator PEF was calculated and personal best PEF was determined as the highest PEF in the previous 2 weeks. The time to plateau was defined as the week beyond which no further improvement occurred. RESULTS: At baseline, average morning PEF was 61% predicted and personal best PEF was 87% predicted. Personal best PEF from twice daily monitoring increased to a plateau of 95% predicted (p<0.0001) after only 3 weeks of budesonide treatment. However, average morning PEF continued to improve for 3 months and "as needed" reliever use for 7 months. CONCLUSIONS: Personal best PEF is a useful concept for asthma self-management plans when determined as the highest PEF over the previous 2 weeks. With twice daily monitoring, personal best PEF reaches plateau levels after only a few weeks of corticosteroid treatment.

Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.

Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae.

An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma, and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control. We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the Australasian population, the increase in morning PEF was 18 L/min and 4 L/min, respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences between the two groups were smaller and not significant. Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained. Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae.

Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids.

To determine predictors for failed reduction of inhaled corticosteroids (ICS), in 50 subjects with well-controlled asthma (age 43.7 [18-69]; 22 males) taking a median dose of 1,000 microg ICS/d (100-3,600 microg/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation test (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflammatory cells were measured at baseline and at monthly intervals. Thirty-nine subjects suffered an asthma exacerbation. Seven subjects were successfully weaned off ICS. Using a Kaplan- Meier survival analysis, the significant predictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive to mannitol during the dose-reduction phase of the study (p = 0.02). Subjects older than 40 yr of age tended to be at greater risk of ICS reduction failure (p = 0.059). Response to mannitol and percentage sputum eosinophils were significantly greater before a failed ICS reduction than before the last successful ICS reduction, whereas there were no significant differences in symptoms, spirometry, or eNO. These findings suggest that documentation of patient's AHR or sputum eosinophils may be useful in guiding the reduction of ICS doses.

Optimal asthma control, starting with high doses of inhaled budesonide.

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1-16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200- and 1,600-microg x day(-1) starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with 3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16 (p=0.03) [corrected]. During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2 occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.