Basil Hetzel Institute for Translational Health Research

Woodville, Australia

Basil Hetzel Institute for Translational Health Research

Woodville, Australia
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van Agteren J.E.,Basil Hetzel Institute for Translational Health Research | Hnin K.,Flinders University | Grosser D.,The Queen Elizabeth Hospital | Carson K.V.,University of Adelaide | Smith B.J.,University of Adelaide
Cochrane Database of Systematic Reviews | Year: 2017

Background: In the recent years, a variety of bronchoscopic lung volume reduction (BLVR) procedures have emerged that may provide a treatment option to participants suffering from moderate to severe chronic obstructive pulmonary disease (COPD). Objectives: To assess the effects of BLVR on the short- and long-term health outcomes in participants with moderate to severe COPD and determine the effectiveness and cost-effectiveness of each individual technique. Search methods: Studies were identified from the Cochrane Airways Group Specialised Register (CAGR) and by handsearching of respiratory journals and meeting abstracts. All searches are current until 07 December 2016. Selection criteria: We included randomized controlled trials (RCTs). We included studies reported as full text, those published as abstract only and unpublished data, if available. Data collection and analysis: Two independent review authors assessed studies for inclusion and extracted data. Where possible, data from more than one study were combined in a meta-analysis using RevMan 5 software. Main results: AeriSeal One RCT of 95 participants found that AeriSeal compared to control led to a significant median improvement in forced expiratory volume in one second (FEV1) (18.9%, interquartile range (IQR) -0.7% to 41.9% versus 1.3%, IQR -8.2% to 12.9%), and higher quality of life, as measured by the St Georges Respiratory Questionnaire (SGRQ) (-12 units, IQR -22 units to -5 units, versus -3 units, IQR -5 units to 1 units), P = 0.043 and P = 0.0072 respectively. Although there was no significant difference in mortality (Odds Ratio (OR) 2.90, 95% CI 0.14 to 62.15), adverse events were more common for participants treated with AeriSeal (OR 3.71, 95% CI 1.34 to 10.24). The quality of evidence found in this prematurely terminated study was rated low to moderate. Airway bypass stents Treatment with airway bypass stents compared to control did not lead to significant between-group changes in FEV1 (0.95%, 95% CI -0.16% to 2.06%) or SGRQ scores (-2.00 units, 95% CI -5.58 units to 1.58 units), as found by one study comprising 315 participants. There was no significant difference in mortality (OR 0.76, 95% CI 0.21 to 2.77), nor were there significant differences in adverse events (OR 1.33, 95% CI 0.65 to 2.73) between the two groups. The quality of evidence was rated moderate to high. Endobronchial coils Three studies comprising 461 participants showed that treatment with endobronchial coils compared to control led to a significant between-group mean difference in FEV1 (10.88%, 95% CI 5.20% to 16.55%) and SGRQ (-9.14 units, 95% CI -11.59 units to -6.70 units). There were no significant differences in mortality (OR 1.49, 95% CI 0.67 to 3.29), but adverse events were significantly more common for participants treated with coils (OR 2.14, 95% CI 1.41 to 3.23). The quality of evidence ranged from low to high. Endobronchial valves Five studies comprising 703 participants found that endobronchial valves versus control led to significant improvements in FEV1 (standardized mean difference (SMD) 0.48, 95% CI 0.32 to 0.64) and scores on the SGRQ (-7.29 units, 95% CI -11.12 units to -3.45 units). There were no significant differences in mortality between the two groups (OR 1.07, 95% CI 0.47 to 2.43) but adverse events were more common in the endobronchial valve group (OR 5.85, 95% CI 2.16 to 15.84). Participant selection plays an important role as absence of collateral ventilation was associated with superior clinically significant improvements in health outcomes. The quality of evidence ranged from low to high. Intrabronchial valves In the comparison of partial bilateral placement of intrabronchial valves to control, one trial favoured control in FEV1 (-2.11% versus 0.04%, P = 0.001) and one trial found no difference between the groups (0.9 L versus 0.87 L, P = 0.065). There were no significant differences in SGRQ scores (MD 2.64 units, 95% CI -0.28 units to 5.56 units) or mortality rates (OR 4.95, 95% CI 0.85 to 28.94), but adverse events were more frequent (OR 3.41, 95% CI 1.48 to 7.84) in participants treated with intrabronchial valves. The lack of functional benefits may be explained by the procedural strategy used, as another study (22 participants) compared unilateral versus partial bilateral placement, finding significant improvements in FEV1 and SGRQ when using the unilateral approach. The quality of evidence ranged between moderate to high. Vapour ablation One study of 69 participants found significant mean between-group differences in FEV1 (14.70%, 95% CI 7.98% to 21.42%) and SGRQ (-9.70 units, 95% CI -15.62 units to -3.78 units), favouring vapour ablation over control. There was no significant between-group difference in mortality (OR 2.82, 95% CI 0.13 to 61.06), but vapour ablation led to significantly more adverse events (OR 3.86, 95% CI 1.00 to 14.97). The quality of evidence ranged from low to moderate. Authors' conclusions: Results for selected BLVR procedures indicate they can provide significant and clinically meaningful short-term (up to one year) improvements in health outcomes, but this was at the expense of increased adverse events. The currently available evidence is not sufficient to assess the effect of BLVR procedures on mortality. These findings are limited by the lack of long-term follow-up data, limited availability of cost-effectiveness data, significant heterogeneity in results, presence of skew and high CIs, and the open-label character of a number of the studies. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Naqvi S.S.,The Queen Elizabeth Hospital | Pollok J.,Basil Hetzel Institute for Translational Health Research | Pollok J.,University of Adelaide | van Agteren J.E.M.,The Queen Elizabeth Hospital | And 7 more authors.
Cochrane Database of Systematic Reviews | Year: 2016

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effectiveness of pharmacological interventions for the treatment of depression in patients with chronic obstructive pulmonary disease (COPD). © 2016 The Cochrane Collaboration.


Pollok J.,Basil Hetzel Institute for Translational Health Research | Pollok J.,University of Adelaide | van Agteren J.E.M.,Basil Hetzel Institute for Translational Health Research | van Agteren J.E.M.,The Queen Elizabeth Hospital | And 6 more authors.
Cochrane Database of Systematic Reviews | Year: 2016

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effectiveness of psychological therapies for the treatment of depression in patients with chronic obstructive pulmonary disease (COPD). © 2016 The Cochrane Collaboration.


van Agteren J.E.M.,Basil Hetzel Institute for Translational Health Research | Carson K.V.,University of Adelaide | Tiong L.U.,The Queen Elizabeth Hospital | Smith B.J.,University of Adelaide
Cochrane Database of Systematic Reviews | Year: 2016

Background: Lung volume reduction surgery (LVRS) performed to treat patients with severe diffuse emphysema was reintroduced in the nineties. Lung volume reduction surgery aims to resect damaged emphysematous lung tissue, thereby increasing elastic properties of the lung. This treatment is hypothesised to improve long-term daily functioning and quality of life, although it may be costly and may be associated with risks of morbidity and mortality. Ten years have passed since the last version of this review was prepared, prompting us to perform an update. Objectives: The objective of this review was to gather all available evidence from randomised controlled trials comparing the effectiveness of lung volume reduction surgery (LVRS) versus non-surgical standard therapy in improving health outcomes for patients with severe diffuse emphysema. Secondary objectives included determining which subgroup of patients benefit from LVRS and for which patients LVRS is contraindicated, to establish the postoperative complications of LVRS and its morbidity and mortality, to determine which surgical approaches for LVRS are most effective and to calculate the cost-effectiveness of LVRS. Search methods: We identified RCTs by using the Cochrane Airways Group Chronic Obstructive Pulmonary Disease (COPD) register, in addition to the online clinical trials registers. Searches are current to April 2016. Selection criteria: We included RCTs that studied the safety and efficacy of LVRS in participants with diffuse emphysema. We excluded studies that investigated giant or bullous emphysema. Data collection and analysis: Two independent review authors assessed trials for inclusion and extracted data. When possible, we combined data from more than one study in a meta-analysis using RevMan 5 software. Main results: We identified two new studies (89 participants) in this updated review. A total of 11 studies (1760 participants) met the entry criteria of the review, one of which accounted for 68% of recruited participants. The quality of evidence ranged from low to moderate owing to an unclear risk of bias across many studies, lack of blinding and low participant numbers for some outcomes. Eight of the studies compared LVRS versus standard medical care, one compared two closure techniques (stapling vs laser ablation), one looked at the effect of buttressing the staple line on the effectiveness of LVRS and one compared traditional 'resectional' LVRS with a non-resectional surgical approach. Participants completed a mandatory course of pulmonary rehabilitation/physical training before the procedure commenced. Short-term mortality was higher for LVRS (odds ratio (OR) 6.16, 95% confidence interval (CI) 3.22 to 11.79; 1489 participants; five studies; moderate-quality evidence) than for control, but long-term mortality favoured LVRS (OR 0.76, 95% CI 0.61 to 0.95; 1280 participants; two studies; moderate-quality evidence). Participants identified post hoc as being at high risk of death from surgery were those with particularly impaired lung function, poor diffusing capacity and/or homogenous emphysema. Participants with upper lobe-predominant emphysema and low baseline exercise capacity showed the most favourable outcomes related to mortality, as investigators reported no significant differences in early mortality between participants treated with LVRS and those in the control group (OR 0.87, 95% CI 0.23 to 3.29; 290 participants; one study), as well as significantly lower mortality at the end of follow-up for LVRS compared with control (OR 0.45, 95% CI 0.26 to 0.78; 290 participants; one study). Trials in this review furthermore provided evidence of low to moderate quality showing that improvements in lung function parameters other than forced expiratory volume in one second (FEV1), quality of life and exercise capacity were more likely with LVRS than with usual follow-up. Adverse events were more common with LVRS than with control, specifically the occurrence of (persistent) air leaks, pulmonary morbidity (e.g. pneumonia) and cardiovascular morbidity. Although LVRS leads to an increase in quality-adjusted life-years (QALYs), the procedure is relatively costly overall. Authors' conclusions: Lung volume reduction surgery, an effective treatment for selected patients with severe emphysema, may lead to better health status and lung function outcomes, specifically for patients who have upper lobe-predominant emphysema with low exercise capacity, but the procedure is associated with risks of early mortality and adverse events. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


News Article | November 21, 2016
Site: www.eurekalert.org

Researchers have made significant progress in the development of a potential vaccine to protect against HIV infection. For the first time, researchers have shown that a combined approach - using a common cold virus to introduce a vaccine into the body, as well as an injection of a DNA-based vaccine - results in the immune system actively protecting against HIV in the gut and bodily cavities. The laboratory studies, conducted so far in mice and now published in the Nature journal Scientific Reports, represent an important step forward in attempts to introduce a first line of defense against HIV at the site of infection. "With sexual activity being one of the primary methods of HIV transmission, it's necessary to try to protect those parts of the body that are most likely to encounter the virus first," says senior author Dr Branka Grubor-Bauk, from the Discipline of Surgery at the University of Adelaide and Basil Hetzel Institute for Translational Health Research, Queen Elizabeth Hospital. "A possible reason why previous HIV vaccine trials have not been successful is because of this lack of a frontline protection. "In mice, we delivered a rhinovirus (or common cold virus) inside the nose, and this virus had been altered to include HIV proteins. At the same time, the mice also received an injection into the skin containing a DNA-based vaccine. This approach resulted in very specific responses in the immune system," Dr Grubor-Bauk says. "Importantly, this vaccine approach encompasses two different arms of the immune system: white blood cells that attack the HIV virus, and specific antibodies that recognize and shut down HIV-positive cells." The Head of the Virology Group conducting this research is Professor Eric Gowans, also from the University's Discipline of Surgery, based at the Basil Hetzel Institute. "There's an element of HIV known as Tat that helps the virus to replicate quite rapidly. One of the beauties of our vaccine approach is that the antibodies inhibit the Tat effect, preventing HIV from replicating itself," Professor Gowans says. "Overall, we found that infection was considerably reduced in the mice we studied. The findings of our work now support the need for further testing of this targeted approach to an HIV vaccine," he says. This study was supported with funding from The Hospital Research Foundation and the National Health and Medical Research Council (NHMRC). The findings are announced ahead of World AIDS Day (Thursday 1 December 2016). Dr Branka Grubor-Bauk Senior Research Officer, Virology Group Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital branka.grubor@adelaide.edu.au Professor Eric Gowans Head, Virology Group Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital eric.gowans@adelaide.edu.au


PubMed | Basil Hetzel Institute for Translational Health Research
Type: | Journal: The Cochrane database of systematic reviews | Year: 2016

Lung volume reduction surgery (LVRS) performed to treat patients with severe diffuse emphysema was reintroduced in the nineties. Lung volume reduction surgery aims to resect damaged emphysematous lung tissue, thereby increasing elastic properties of the lung. This treatment is hypothesised to improve long-term daily functioning and quality of life, although it may be costly and may be associated with risks of morbidity and mortality. Ten years have passed since the last version of this review was prepared, prompting us to perform an update.The objective of this review was to gather all available evidence from randomised controlled trials comparing the effectiveness of lung volume reduction surgery (LVRS) versus non-surgical standard therapy in improving health outcomes for patients with severe diffuse emphysema. Secondary objectives included determining which subgroup of patients benefit from LVRS and for which patients LVRS is contraindicated, to establish the postoperative complications of LVRS and its morbidity and mortality, to determine which surgical approaches for LVRS are most effective and to calculate the cost-effectiveness of LVRS.We identified RCTs by using the Cochrane Airways Group Chronic Obstructive Pulmonary Disease (COPD) register, in addition to the online clinical trials registers. Searches are current to April 2016.We included RCTs that studied the safety and efficacy of LVRS in participants with diffuse emphysema. We excluded studies that investigated giant or bullous emphysema.Two independent review authors assessed trials for inclusion and extracted data. When possible, we combined data from more than one study in a meta-analysis using RevMan 5 software.We identified two new studies (89 participants) in this updated review. A total of 11 studies (1760 participants) met the entry criteria of the review, one of which accounted for 68% of recruited participants. The quality of evidence ranged from low to moderate owing to an unclear risk of bias across many studies, lack of blinding and low participant numbers for some outcomes. Eight of the studies compared LVRS versus standard medical care, one compared two closure techniques (stapling vs laser ablation), one looked at the effect of buttressing the staple line on the effectiveness of LVRS and one compared traditional resectional LVRS with a non-resectional surgical approach. Participants completed a mandatory course of pulmonary rehabilitation/physical training before the procedure commenced. Short-term mortality was higher for LVRS (odds ratio (OR) 6.16, 95% confidence interval (CI) 3.22 to 11.79; 1489 participants; five studies; moderate-quality evidence) than for control, but long-term mortality favoured LVRS (OR 0.76, 95% CI 0.61 to 0.95; 1280 participants; two studies; moderate-quality evidence). Participants identified post hoc as being at high risk of death from surgery were those with particularly impaired lung function, poor diffusing capacity and/or homogenous emphysema. Participants with upper lobe-predominant emphysema and low baseline exercise capacity showed the most favourable outcomes related to mortality, as investigators reported no significant differences in early mortality between participants treated with LVRS and those in the control group (OR 0.87, 95% CI 0.23 to 3.29; 290 participants; one study), as well as significantly lower mortality at the end of follow-up for LVRS compared with control (OR 0.45, 95% CI 0.26 to 0.78; 290 participants; one study). Trials in this review furthermore provided evidence of low to moderate quality showing that improvements in lung function parameters other than forced expiratory volume in one second (FEVLung volume reduction surgery, an effective treatment for selected patients with severe emphysema, may lead to better health status and lung function outcomes, specifically for patients who have upper lobe-predominant emphysema with low exercise capacity, but the procedure is associated with risks of early mortality and adverse events.

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