Epidemiology and microbiology of severe community-acquired pneumonia in Central Australia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) has high mortality and morbidity. AIMS: To describe the epidemiology and microbiology of SCAP in Central Australia. METHODS: A retrospective epidemiological study describing the characteristics, incidence rates (IR) and microbiological aetiology of SCAP in Central Australia. Adult patients admitted to Alice Springs Hospital Intensive Care Unit (ICU) between 2011 and 2014 that fitted the Infectious Diseases Society of America and American Thoracic Society definition of SCAP were included. Medical records were reviewed and compared between indigenous and non-indigenous patients. Primary outcomes were incidence rate and microbiological aetiology of SCAP. Secondary outcomes were 30-day mortality, and ICU and hospital length of stay (LoS). RESULTS: A total of 185 patents were included (156 indigenous; 29 non-indigenous). The overall SCAP IR per 1000 person-years was 3.24 (3.75 indigenous; 1.87 non-indigenous) with an IR difference of 2.71 after adjustment (P < 0.001). Those aged ≥50 years had an IR 74.8% higher than those younger. Male IR was 50% higher than females. There was a significant difference between indigenous and non-indigenous groups for age (48 vs 64 years), but not for 30-day mortality (7.7% vs 10.3%), ICU LoS (4.8 vs 4.6 days) and hospital LoS (10.9 vs 15.1 days) respectively. Likely causative pathogen(s) were identified in 117 patients; Streptococcus pneumoniae was the most common pathogen (28.2%), followed by Haemophilus influenzae (19.7%), Influenza A/B (16.2%) and Staphylococcus aureus (14.5%). CONCLUSION: A high incidence of SCAP was observed in Central Australia, disproportionately affecting the indigenous population. Prevention strategies are imperative, as well as early identification of SCAP and appropriate empiric antibiotic regimens.

Pharmacological and surgical interventions for the treatment of gastro-oesophageal reflux in adults and children with asthma.

BACKGROUND: Asthma and gastro-oesophageal reflux disease (GORD) are common medical conditions that frequently co-exist. GORD has been postulated as a trigger for asthma; however, evidence remains conflicting. Proposed mechanisms by which GORD causes asthma include direct airway irritation from micro-aspiration and vagally mediated oesophagobronchial reflux. Furthermore, asthma might precipitate GORD. Thus a temporal association between the two does not establish that GORD triggers asthma. OBJECTIVES: To evaluate the effectiveness of GORD treatment in adults and children with asthma, in terms of its benefits for asthma. SEARCH METHODS: The Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and online clinical trial databases were searched. The most recent search was conducted on 23 June 2020. SELECTION CRITERIA: We included randomised controlled trials comparing treatment of GORD in adults and children with a diagnosis of both asthma and GORD versus no treatment or placebo. DATA COLLECTION AND ANALYSIS: A combination of two independent review authors extracted study data and assessed trial quality. The primary outcome of interest for this review was acute asthma exacerbation as reported by trialists. MAIN RESULTS: The systematic search yielded a total of 3354 citations; 23 studies (n = 2872 participants) were suitable for inclusion. Included studies reported data from participants in 25 different countries across Europe, North and South America, Asia, Australia, and the Middle East. Participants included in this review had moderate to severe asthma and a diagnosis of GORD and were predominantly adults presenting to a clinic for treatment. Only two studies assessed effects of intervention on children, and two assessed the impact of surgical intervention. The remainder were concerned with medical intervention using a variety of dosing protocols. There was an uncertain reduction in the number of participants experiencing one or more moderate/severe asthma exacerbations with medical treatment for GORD (odds ratio 0.53, 95% confidence interval (CI) 0.17 to 1.63; 1168 participants, 2 studies; low-certainty evidence). None of the included studies reported data related to the other primary outcomes for this review: hospital admissions, emergency department visits, and unscheduled doctor visits. Medical treatment for GORD probably improved forced expiratory volume in one second (FEV1) by a small amount (mean difference (MD) 0.10 L, 95% CI 0.05 to 0.15; 1333 participants, 7 studies; moderate-certainty evidence) as well as use of rescue medications (MD -0.71 puffs per day, 95% CI -1.20 to -0.22; 239 participants, 2 studies; moderate-certainty evidence). However, the benefit of GORD treatment for morning peak expiratory flow rate was uncertain (MD 6.02 L/min, 95% CI 0.56 to 11.47; 1262 participants, 5 studies). It is important to note that these mean improvements did not reach clinical importance. The benefit of GORD treatment for outcomes synthesised narratively including benefits of treatment for asthma symptoms, quality of life, and treatment preference was likewise uncertain. Data related to adverse events with intervention were generally underreported by the included studies, and those that were available indicated similar rates regardless of allocation to treatment or placebo. AUTHORS' CONCLUSIONS: Effects of GORD treatment on the primary outcomes of number of people experiencing one or more exacerbations and hospital utilisation remain uncertain. Medical treatment for GORD in people with asthma may provide small benefit for a number of secondary outcomes related to asthma management. This review determined with moderate certainty that with treatment, lung function measures improved slightly, and use of rescue medications for asthma control was reduced. Further, evidence is insufficient to assess results in children, or to compare surgery versus medical therapy.

Pragmatic randomised controlled trial of a personalised intervention for carers of people requiring home oxygen therapy.

We used a pragmatic randomised controlled trial to evaluate a behavioural change strategy targeting carers of chronically hypoxaemic patients using long-term home oxygen therapy. Intervention group carers participated in personalised educational sessions focusing on motivating carers to take actions to assist patients. All patients received usual care. Effectiveness was measured through a composite event of patient survival to hospitalisation, residential care admission or death to 12 months. Secondary outcomes at baseline, 3, 6 and 12 months included carer and patient emotional and physical well-being. No difference between intervention (n = 100) and control (n = 97) patients was found for the composite outcome (hazard ratio (HR) 1.22, 95% confidence interval (CI) = 0.89, 1.68; p = 0.22). Improved fatigue, mastery, vitality and general health occurred in intervention group patients (all p values < 0.05). No benefits were seen in carer outcomes. Mortality was significantly higher in intervention patients (HR = 2.01, 95% CI = 1.00, 4.14; p = 0.05; adjusted for Australia-modified Karnofsky Performance Status), with a significant diagnosis-intervention interaction (p = 0.028) showing higher mortality in patients with COPD (HR 4.26; 95% CI = 1.60, 11.35) but not those with interstitial lung disease (HR 0.83; 95% CI = 0.28, 2.46). No difference was detected in the primary outcome, but patient mortality was higher when carers had received the intervention, especially in the most disabled patients. Trials examining behavioural change interventions in severe disease should stratify for functionality, and both risks and benefits should be independently monitored. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12607000177459).

Bronchoscopic lung volume reduction procedures for chronic obstructive pulmonary disease.

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: AeriSealOne 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 stentsTreatment 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 coilsThree 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 valvesFive 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 valvesIn 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 ablationOne 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.

Mass media interventions for preventing smoking in young people.

BACKGROUND: Mass media interventions can be used as a way of delivering preventive health messages. They have the potential to reach and modify the knowledge, attitudes and behaviour of a large proportion of the community. OBJECTIVES: To assess the effects of mass media interventions on preventing smoking in young people, and whether it can reduce smoking uptake among youth (under 25 years), improve smoking attitudes, intentions and knowledge, improve self-efficacy/self-esteem, and improve perceptions about smoking, including the choice to follow positive role models. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, with additional searches of MEDLINE and Embase in June 2016. This is an update of a review first published in 1998. SELECTION CRITERIA: Randomized trials, controlled trials without randomization and interrupted time-series studies that assessed the effect of mass media campaigns (defined as channels of communication such as television, radio, newspapers, social media, billboards, posters, leaflets or booklets intended to reach large numbers of people and which are not dependent on person-to-person contact) in influencing the smoking behaviour (either objective or self-reported) of young people under the age of 25 years. We define smoking behaviour as the presence or absence of tobacco smoking or other tobacco use, or both, and the frequency of tobacco use. Eligible comparators included education or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted information relating to the characteristics and the content of media interventions, participants, outcomes, methods of the study and risks of bias. We combined studies using qualitative narrative synthesis. We assessed the risks of bias for each study using the Cochrane 'Risk of bias' tool, alongside additional domains to account for the nature of the intervention. We assessed the quality of evidence contributing to outcomes using GRADE. MAIN RESULTS: We identified eight eligible studies reporting information about mass media smoking campaigns, one of which is new for this update. Seven of the studies used a controlled trial design and one an interrupted time-series analysis. Risks of bias were high across all included studies and there was considerable heterogeneity in study design, intervention and population being assessed.Three studies (n = 17,385), one of which compared a mass media intervention to no intervention and two of which evaluated mass media interventions as adjuncts to school-based interventions, found that the mass media interventions reduced the smoking behaviour of young people. The remaining five studies (n = 72,740) did not detect a significant effect on smoking behaviour. These included three studies comparing a mass media intervention to no intervention, one study evaluating a mass media intervention as an adjunct to a school-based intervention, and one interrupted time-series study of a social media intervention. The three campaigns which found a significant effect described their theoretical basis, used formative research in designing the campaign messages, and used message broadcast of reasonable intensity over extensive periods of time. However, some of the campaigns which did not detect an effect also exhibited these characteristics. Effective campaigns tended to last longer (minimum 3 years) and were more intense (more contact time) for both school-based lessons (minimum eight lessons per grade) and media spots (minimum four weeks' duration across multiple media channels with between 167 and 350 TV and radio spots). Implementation of combined school-based components (e.g. school posters) and the use of repetitive media messages delivered by multiple channels (e.g. newspapers, radio, television) appeared to contribute to successful campaigns. AUTHORS' CONCLUSIONS: Certainty about the effects of mass media campaigns on smoking behaviour in youth is very low, due to inconsistency between studies in both design and results, and due to methodological issues amongst the included studies. It would therefore be unwise to offer firm conclusions based on the evidence in this review. Methodologically rigorous studies investigating the effect of social media and novel forms of technology as part of tobacco prevention campaigns for youth are needed.

Prolonged antibiotics for non-cystic fibrosis bronchiectasis in children and adults.

BACKGROUND: The vicious cycle hypothesis for bronchiectasis predicts that bacterial colonisation of the respiratory tract perpetuates inflammatory change. This damages the mucociliary escalator, preventing bacterial clearance and allowing persistence of pro-inflammatory mediators. Conventional treatment with physiotherapy and intermittent antibiotics is believed to improve the condition of people with bronchiectasis, although no conclusive data show that these interventions influence the natural history of the condition. Various strategies have been tried to interrupt this cycle of infection and inflammation, including prolonging antibiotic treatment with the goal of allowing the airway mucosa to heal. OBJECTIVES: To determine the benefits of prolonged antibiotic therapy in the treatment of patients with bronchiectasis. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and reference lists of identified articles. Searches were current as of February 2014. SELECTION CRITERIA: Randomised trials examining the use of prolonged antibiotic therapy (for four or more weeks) in the treatment of bronchiectasis compared with placebo or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors to ask for missing information. MAIN RESULTS: Eighteen trials met the inclusion criteria, randomly assigning a total of 1157 participants. Antibiotics were given for between four weeks and 83 weeks. Limited meta-analysis was possible because of the diversity of outcomes reported in these trials. Based on the number of participants with at least one exacerbation, the meta-analysis showed significant effects in favour of the intervention (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.19 to 0.52; P value < 0.00001), with events occurring in 271 per 1000 people in the intervention arm (95% CI 126 to 385) and in 546 per 1000 in the control population, based on evidence of moderate quality. A non-statistically significant reduction in hospitalisation favoured the use of prolonged antibiotics with a moderate quality grade of supporting evidence (37 per 1000 in the intervention arm (95% CI 13 to 96) and 87 per 1000 in control (OR 0.40, 95% CI 0.14 to 1.11; P value = 0.08). Drug resistance developed in 36 of 220 participants taking antibiotics compared with 10 of 211 participants given placebo or standard therapy (OR 3.48, 95% CI 1.20 to 10.07; P value = 0.02), translating to natural frequencies of 155 per 1000 in the intervention arm (95% CI 59 to 346) and 50 per 1000 in the control arm. The intervention was well tolerated with no overall significant difference in withdrawal between treatment and placebo groups (OR 0.91, 95% CI 0.56 to 1.49). Diarrhoea was commonly reported as an adverse event, particularly with an oral intervention. AUTHORS' CONCLUSIONS: Available evidence shows benefit associated with use of prolonged antibiotics in the treatment of patients with bronchiectasis, at least halving the odds of exacerbation (with 275 fewer exacerbations per every 1000 people treated in the antibiotic arm compared with the control arm) and hospitalisation (50 fewer hospitalisations per 1000 people in the antibiotic arm compared with the control arm). However, the risk of emerging drug resistance is increased more than threefold. This review is limited by diversity of trials and by evidence of moderate to low quality. Further randomised controlled trials with adequate power and standardised end points are required.

Safety of varenicline tartrate and counseling versus counseling alone for smoking cessation: a randomized controlled trial for inpatients (STOP study).

INTRODUCTION: Inpatient medical settings offer an opportunistic environment for initiating smoking cessation interventions to patients reflecting on their health. Current evidence has shown the superior efficacy of varenicline tartrate (VT) for smoking cessation compared with other tobacco cessation therapies; however, recent evidence also has highlighted concerns about the safety and tolerability of VT. Given these apprehensions, we aimed to evaluate the safety and effectiveness of VT plus quitline-counseling compared to quitline-counseling alone in the inpatient medical setting. METHODS: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to 3 hospitals were randomized to receive either 12 weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice daily) plus quitline-counseling (VT+C), (n = 196) or quitline-counseling alone (n = 196). RESULTS: VT was well tolerated in the inpatient setting among subjects admitted with acute smoking-related illnesses (mean age 52.8±2.89 and 53.7±2.77 years in the VT+C and counseling alone groups, respectively). The most common self-reported adverse event during the 12-week treatment phase was nausea (16.3% in the VT+C group compared with 1.5% in the counseling alone group). Thirteen deaths occurred during the study period (n = 6 were in the VT+C arm compared with n = 7 in the counseling alone arm). All of these subjects had known comorbidities or developed underlying comorbidities. CONCLUSIONS: VT appears to be a safe and well-tolerated opportunistic treatment for inpatient smokers who have related chronic disease. Based on the proven efficacy of varenicline from outpatient studies and our recent inpatient evidence, we suggest it be considered as part of standard care in the hospital setting.

The Association of Obstructive Sleep Apnea in Ischemia with No Obstructive Coronary Artery Disease - A Pilot Study.

Obstructive sleep apnea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This pilot study assessed the association of OSA and invasive coronary microvascular function in patients with ischemia with no obstructive coronary artery disease (INOCA). Forty-two patients with angina, were prospectively screened at a single tertiary centre covering the northern metropolitan area of South Australia, from February 2018 to December 2020 (ACTRN12618000149268). Forty patients were invited into to this observational study after coronary angiography demonstrated INOCA and functional coronary vasomotor disorder (n = 40). Twenty one participants subsequently underwent a sleep study for OSA diagnosis while 9 participants had prior formal diagnosis of OSA (ACTRN12618000227291). Of the 30 participants with OSA data, 87% (n = 26) had a diagnosis of OSA. Accordingly, 11 with mild severity, 7 with moderate severity and 8 with severe OSA. No OSA was observed in 4 participants. Participants with OSA were older [61.4±8.7 vs 49.9±9.7, P = 0.002] with similar clinical characteristics for the pattern and severity of angina and other co-morbidities. 73.3% (n = 22) had abnormal functional disorders of the epicardial coronary arteries and/or coronary microcirculation. On multivariate analysis, OSA was the only statistically significant association with functional coronary microvascular disorders [OR 53.95, 1.41 -2065.01, P = 0.032]. This study provided an observation of a significant correlation between INOCA with abnormal coronary vasomotor function and OSA in an Australian cohort. This correlation supports a possible pathophysiological interplay between these two conditions that needs to be further evaluated. The benefit of treatment of OSA in this subset remains unknown.

Correction: Two-year efficacy of varenicline tartrate and counselling for inpatient smoking cessation (STOP study): A randomized controlled clinical trial.

[This corrects the article DOI: 10.1371/journal.pone.0231095.].

Two-year efficacy of varenicline tartrate and counselling for inpatient smoking cessation (STOP study): A randomized controlled clinical trial.

INTRODUCTION: Varenicline tartrate is superior for smoking cessation to other tobacco cessation therapies by 52 weeks, in the outpatient setting. We aimed to evaluate the long-term (104 week) efficacy following a standard course of inpatient-initiated varenicline tartrate plus Quitline-counselling compared to Quitline-counselling alone. METHODS: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to one of three hospitals, were randomised to receive either 12-weeks of varenicline tartrate (titrated from 0.5mg daily to 1mg twice-daily) plus Quitline-counselling, (n = 196) or Quitline-counselling alone, (n = 196), with continuous abstinence from smoking assessed at 104 weeks. RESULTS: A total of 1959 potential participants were screened for eligibility between August 2008 and December 2011. The proportion of participants who remained continuously abstinent (intention-to-treat) at 104 weeks were significantly greater in the varenicline tartrate plus counselling arm (29.2% n = 56) compared to counselling alone (18.8% n = 36; p = 0.02; odds ratio 1.78; 95%CI 1.10 to 2.86, p = 0.02). Twenty-two deaths occurred during the 104 week study (n = 10 for varenicline tartrate plus counselling and n = 12 for Quitline-counselling alone). All of these participants had known or developed underlying co-morbidities. CONCLUSIONS: This is the first study to examine the efficacy and safety of varenicline tartrate over 104 weeks within any setting. Varenicline tartrate plus Quitline-counselling was found to be an effective opportunistic treatment when initiated for inpatient smokers who had been admitted with tobacco-related disease.

The impact of ethnicity on the prevalence and severity of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common disorder associated with multiple adverse health consequences and its prevalence is increasing in parallel with rising obesity trends. Early support for ethnic differences in OSA prevalence and severity has been derived from studies of relatively homogenous ethnic groups. However, between-study comparisons are problematic given differing methodologies. Recent large inter-ethnic studies examining different ethnic populations using standardized protocols support the notion that Chinese have an increased OSA prevalence and severity compared to those of European descent. Although the evidence is less clear, some data suggest that Hispanic/Mexican Americans also show higher rates of OSA, while OSA prevalence in African Americans is not dissimilar to that of populations of European ancestry. Of the anatomical traits underlying differences in OSA prevalence and severity between ethnic groups (i.e., obesity, fat distribution, and craniofacial structure) obesity appears to be the most important. The effect of ethnicity on non-anatomical factors (i.e., upper airway muscle responsiveness, arousal threshold, and loop gain) responsible for OSA severity and potentially prevalence is currently unknown and needs further research.