Protocol: inspiratory muscle training for promoting recovery and outcomes in ventilated patients (IMPROVe): a randomised controlled trial

Introduction: Inspiratory muscle weakness is a known consequence of mechanical ventilation and a potential contributor to difficulty in weaning from ventilatory support. Inspiratory muscle training (IMT) reduces the weaning period and increases the likelihood of successful weaning in some patients. However, it is not known how this training affects the residual inspiratory muscle fatigability following successful weaning nor patients' quality of life or functional outcomes. Methods and analysis: This dual centre study includes two concurrent randomised controlled trials of IMT in adult patients who are either currently ventilator-dependent (>7 days) (n=70) or have been recently weaned from mechanical ventilation (>7 days) in the past week (n=70). Subjects will be stable, alert and able to actively participate and provide consent. There will be concealed allocation to either treatment (IMT) or usual physiotherapy (including deep breathing exercises without a resistance device). Primary outcomes are inspiratory muscle fatigue resistance and maximum inspiratory pressures. Secondary outcomes are quality of life (Short Form-36v2, EQ-5D), functional status (Acute Care Index of Function), rate of perceived exertion (Borg Scale), intensive care length of stay (days), post intensive care length of stay (days), rate of reintubation (%) and duration of ventilation (days). Ethics and dissemination: Ethics approval has been obtained from relevant institutions, and results will be published with a view to influencing physiotherapy practice in the management of long-term ventilator-dependent patients to accelerate weaning and optimise rehabilitation outcomes

The efficacy and safety of adrenergic blockade post burn injury: a systematic review and meta-analysis

BACKGROUND The hypermetabolic state after severe burns is a major problem that can lead to several pathophysiologic changes and produce multiple sequelae. Adrenergic blockade has been widely used to reverse these changes and improve outcomes in burned patients but has not been rigorously evaluated. The aim of this systematic review was to investigate the efficacy and safety of the use of adrenergic blockade after burn injury

Exercise and the Prevention of Oesophageal Cancer (EPOC) study protocol: a randomized controlled trial of exercise versus stretching in males with Barrett's oesophagus

<p>Abstract</p> <p>Background</p> <p>Chronic gastro-oesophageal reflux disease and excessive body fat are considered principal causes of Barrett's oesophagus (a metaplastic change in the cells lining the oesophagus) and its neoplastic progression, oesophageal adenocarcinoma. Metabolic disturbances including altered levels of obesity-related cytokines, chronic inflammation and insulin resistance have also been associated with oesophageal cancer development, especially in males. Physical activity may have the potential to abrogate metabolic disturbances in males with Barrett's oesophagus and elicit beneficial reductions in body fat and gastro-oesophageal reflux symptoms. Thus, exercise may be an effective intervention in reducing oesophageal adenocarcinoma risk. However, to date this hypothesis remains untested.</p> <p>The 'Exercise and the Prevention of Oesophageal Cancer Study' will determine whether 24 weeks of exercise training will lead to alterations in risk factors or biomarkers for oesophageal adenocarcinoma in males with Barrett's oesophagus. Our primary outcomes are serum concentrations of leptin, adiponectin, tumour necrosis factor-alpha, C-reactive protein and interleukin-6 as well as insulin resistance. Body composition, gastro-oesophageal reflux disease symptoms, cardiovascular fitness and muscular strength will also be assessed as secondary outcomes.</p> <p>Methods/Design</p> <p>A randomized controlled trial of 80 overweight or obese, inactive males with Barrett's oesophagus will be conducted in Brisbane, Australia. Participants will be randomized to an intervention arm (60 minutes of moderate-intensity aerobic and resistance training, five days per week) or a control arm (45 minutes of stretching, five days per week) for 24 weeks. Primary and secondary endpoints will be measured at baseline (week 0), midpoint (week 12) and at the end of the intervention (week 24).</p> <p>Discussion</p> <p>Due to the increasing incidence and very high mortality associated with oesophageal adenocarcinoma, interventions effective in preventing the progression of Barrett's oesophagus are urgently needed. We propose that exercise may be successful in reducing oesophageal adenocarcinoma risk. This primary prevention trial will also provide information on whether the protective association between physical activity and cancer is causal.</p> <p>Trial Registration</p> <p>ACTRN12609000401257</p

The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial

Objective: To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development. Methods: A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions) versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions) in inactive, overweight/obese (25.0-34.9 kg/m2) males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance HOMA). Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value. Results: Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80); 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control) was observed for waist circumference (-4.5 95%CI -7.5, -1.4 cm; p &lt; 0.01). Effects on primary outcomes were not statistically significant. Conclusion: This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000401257. © 2015 Winzer et al

Efficacy and safety of normal saline instillation: A systematic review

Objective: To investigate the efficacy and safety of the technique of instillation of normal saline prior to suction of airways in intubated patients. Data sources: Databases searched included: MEDLINE, CINAHL, EMBASE, Cochrane Controlled Trials Register and Full text clinicians' health journals @ Ovid from the earliest time to March 2009. Citation tracking of relevant primary and review articles. Review methods: All randomised controlled trials, crossover trials, quasi- and full systematic reviews were screened. From 65 articles screened, 17 articles (two quasi-systematic reviews and 15 empirical studies) met the eligibility criteria and were included for data extraction. The outcomes in the reviewed studies included oxygenation, lung mechanics, sputum yield, dyspnoea, tube patency and ventilator-associated pneumonia. Effect sizes and 95% confidence intervals were calculated. Results: Studies were mainly of low methodological quality due to factors such as lack of assessor blinding and within-group-only statistics. Overall, there was a positive effect favouring the use of saline to increase sputum yield (d=0.50, 95% confidence interval 0.10 to 0.90). Due to heterogeneity of methodology, it was not possible to perform meta-analyses on haemodynamics, oxygenation, tube patency and ventilator-associated pneumonia. Overall, while a decrease was found in oxygen saturation measured by pulse oximetry (SpO) following instillation of normal saline compared with no saline, this was of limited clinical significance. Conclusions: The results of this review reflect the poor quality of available articles on instillation of normal saline prior to suction of artificial airways. There is little evidence of benefit but also minimal evidence of safety risks. Controlled trials of better quality and more clinically relevant outcomes need to be performed before this technique is either accepted or rejected

Continuous infusion of time-dependent antibiotics: lung pharmacokinetics and pharmacodynamics

Lung infections continue to represent a significant burden to the healthcare system and improved antibiotic therapy may serve as a means to improve patient outcomes. Time-dependent antibiotics such as [beta]-lactams and glycopeptides are commonly used as therapy for lung infections, and the emerging data suggest that administration by continuous infusion may result in improved patient outcomes. The aim of this review is to identify and analyze the published literature on lung penetration of time-dependent antibiotics administered by continuous infusion. Although only 16 relevant articles were identified during this structured review, data suggest that continuous infusion may have an important role in therapy for various lung infections. In acute lung injury, such as pneumonia, where local inflammation causes tight junctions between alveolar membrane epithelial cells to open, antibiotic penetration is significant. Continuous infusion of time-dependent antibiotics in these patients results in higher trough concentrations than bolus administration that optimizes the pharmacodynamic properties of these antibiotics. In chronic lung injuries, as evidenced in cystic fibrosis and chronic bronchitis, fibrotic scarring and the presence of thick mucus leads to highly variable but significantly reduced antibiotic penetration. In the presence of such pathology, continuous infusion of these antibiotics seems to normalize variable pharmacokinetic parameters as well as result in higher trough concentrations compared with bolus administration. Continuous infusion of time-dependent antibiotics seems to be a suitable method for optimizing antibiotic concentrations at the site of lung infections and as a result may lead to improved treatment success

Muscle strength assessment in critically ill patients with handheld dynamometry: an investigation of reliability, minimal detectable change, and time to peak force generation

Purpose: Dynamometry is an objective tool for volitional strength evaluation that may overcome the limited sensitivity of the Medical Research Council scale for manual muscle tests, particularly at grades 4 and 5. The primary aims of this study were to investigate the reliability, minimal detectable change, and time to peak muscle force, measured with portable dynamometry, in critically ill patients. Materials and methods: Isometric hand grip, elbow flexion, and knee extension were measured with portable dynamometry. Results: Interrater consistency (intraclass correlation coefficient [95% confidence interval]) (0.782 [0.321-0.930] to 0.946 [0.840-0.982]) and test-retest agreement (0.819 [0.390-0.943] to 0.918 [0.779-0.970]) were acceptable for all dynamometry forces, with the exception of left elbow flexion. Despite generally good reliability, a mean change (upper 95% confidence interval) of 2.8 (7.8) kg, 1.9 (5.2) kg, and 2.6(7.1) kg may be required from a patient's baseline force measurement of right grip, elbow flexion, and knee extension to reflect real force changes. There was also a delay in the time for critically ill patients to generate peak muscle forces, compared with healthy controls (P ≤ .001). Conclusions: Dynamometry can provide reliable measurements in alert critically ill patients, but moderate changes in strength may be required to overcome measurement error, during the acute recovery period. Deficits in force timing may reflect impaired neuromuscular control

Peripheral muscle strength training in COPD* - A systematic review

Background: Skeletal muscle weakness, and the associated impact on exercise tolerance, provides a strong theoretical rationale for strength training intervention for people with COPD. Aim: The purpose of this review was to examine systematically the current evidence for peripheral muscle strength training in people with COPD. Method: Empirical trials and reviews relating to strength training in COPD were obtained by searching electronic databases and citation tracking, using the keywords of COPD with strength/resistance training and skeletal muscle. Two reviewers completed data extraction and quality assessment independently, using the PEDro (physiotherapy evidence database) scale and a checklist for review articles. Effect sizes and 95% confidence intervals were determined for empiric trials and metaanalysis used where appropriate. Results: The search strategy yielded 13 articles (9 empirical trials and 4 reviews). Strength training was found to have strong evidence for improving upper body and leg strength. However, no strong evidence for strength training was found for other outcome measures. Conclusions: Further research is required to investigate the effects of strength training on functional activities, such as balance, upper limb function, self care, and participation in daily life