Saline at lower tonicity in cystic fibrosis (SALTI-CF) trial comparing 0.9% versus 3% versus 6% nebulised saline.

BACKGROUND: In people with cystic fibrosis (CF), regular nebulisation of 6% or 7% saline improves lung function; however, these concentrations are not always tolerable. Clinically, some CF patients report using lower concentrations of saline to improve tolerability, yet the effects of lower concentrations are unknown. This study therefore aimed to evaluate the relative effectiveness and tolerability of 0.9% versus 3% versus 6% saline nebulised twice daily with an eFlow rapid nebuliser. METHODS: This was a randomised, blinded, placebo-controlled, parallel-group, multicentre study where subjects inhaled 4 mL of 0.9%, 3% or 6% saline twice daily for 16 weeks. The primary outcome was forced expiratory volume in 1 s. The secondary outcomes were: forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC; quality of life; exercise capacity; acquisition or loss of bacterial organisms in expectorated sputum; tolerability of nebulised saline; pulmonary exacerbations; and adverse events. RESULTS: 140 participants were randomised to 0.9% (n=47), 3% (n=48) or 6% (n=45) saline. 134 participants (96%) contributed to the intention-to-treat analysis. 3% saline significantly improved lung function and increased the time to first pulmonary exacerbation compared with 0.9% saline but did not improve quality of life. 6% saline had similar benefits to 3% saline but also significantly improved quality of life compared with 3% saline. Only 6% saline delayed the time to intravenous antibiotics for pulmonary exacerbation. Tolerability and adherence were similar. CONCLUSIONS: Dilution of 6% saline to 3% maintains the benefits for lung function and exacerbation prevention; however, the positive impacts of 6% saline on quality of life and time to i.v. antibiotics for pulmonary exacerbations are lost.

Reporting characteristics of journal infographics: a cross-sectional study.

BACKGROUND: Infographics have become an increasingly popular method to present research findings and increase the attention research receives. As many scientific journals now use infographics to boost the visibility and uptake of the research they publish, infographics have become an important tool for medical education. It is unknown whether such infographics convey the key characteristics that are needed to make useful interpretations of the data such as an adequate description of the study population, interventions, comparators and outcomes; methodological limitations; and numerical estimates of benefits and harms. This study described whether infographics published in peer-reviewed health and medical research journals contain key characteristics that are needed to make useful interpretations of clinical research. METHODS: In this cross-sectional study, we identified peer-reviewed journals listed in the top quintile of 35 unique fields of medicine and health research listed in the Journal Citation Reports database. Two researchers screened journals for the presence of infographics. We defined an infographic as a graphical visual representation of research findings. We extracted data from a sample of two of the most recent infographics from each journal. Outcomes were the proportion of infographics that reported key characteristics such as study population, interventions, comparators and outcomes, benefits, harms, effect estimates with measures of precision, between-group differences and conflicts of interest; acknowledged risk of bias, certainty of evidence and study limitations; and based their conclusions on the study's primary outcome. RESULTS: We included 129 infographics from 69 journals. Most infographics described the population (81%), intervention (96%), comparator (91%) and outcomes (94%), but fewer contained enough information on the population (26%), intervention (45%), comparator (20%) and outcomes (55%) for those components of the study to be understood without referring to the main paper. Risk of bias was acknowledged in only 2% of infographics, and none of the 69 studies that had declared a conflict of interest disclosed it in the infographics. CONCLUSIONS: Most infographics do not report sufficient information to allow readers to interpret study findings, including the study characteristics, results, and sources of bias. Our results can inform initiatives to improve the quality of the information presented in infographics.

How do people use and view infographics that summarise health and medical research? A cross-sectional survey.

BACKGROUND: Understanding how people use infographics and their opinion on them has important implications for the design of infographics but has not been investigated. The aim of this study was to describe people's use of and opinions about infographics summarising health and medical research, preferences for information to include in infographics, and barriers to reading full-text articles. METHODS: We conducted an online cross-sectional survey of consumers of infographics that summarise health or medical research. Demographic and outcome data were collected and summarised using descriptive statistics. A sensitivity analysis explored whether being a researcher/academic influenced the findings. RESULTS: Two hundred fifty-four participants completed the survey (88% completion rate). Participants included health professionals (66%), researchers (34%), academics (24%), and patients/the public (13%). Most used Twitter (67%) and smartphones (89%) to access and view infographics, and thought infographics were useful tools to communicate research (92%) and increase the attention research receives (95%). Although most participants were somewhat/extremely likely (76%) to read the full-text article after viewing an infographic, some used infographics as a substitute for the full text at least half of the time (41%), thought infographics should be detailed enough so they do not have to read the full text (55%), and viewed infographics as tools to reduce the time burden of reading the full text (64%). Researchers/academics were less likely to report behaviours/beliefs suggesting infographics can reduce the need to read the full-text article. CONCLUSIONS: Given many people use infographics as a substitute for reading the full-text article and want infographics to be detailed enough so they don't have to read the full text, a checklist to facilitate clear, transparent, and sufficiently detailed infographics summarising some types of health and medical research may be useful.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings. Date of the most recent search: 12 October 2020. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.  DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Timing of hypertonic saline inhalation for cystic fibrosis.

BACKGROUND: Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. SEARCH METHODS: We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 28 February 2019. SELECTION CRITERIA: Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the trials identified by the search for potential inclusion in the review. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: The searches identified 104 trial reports which represented 51 trials, of which three cross-over trials (providing data on 77 participants) met our inclusion criteria. We present three comparisons: inhalation before versus during airway clearance techniques; inhalation before versus after airway clearance techniques; and inhalation during versus after airway clearance techniques. One trial (50 participants), given its three-arm design, was eligible for all three comparisons. No trials compared morning versus evening inhalation of hypertonic saline. The evidence from the three trials was judged to be of low quality downgraded for limitations (high risk of bias due to blinding) and indirectness (all participants are adults, and therefore not applicable to children). Intervention periods ranged from one treatment to three treatments in one day. There were no clinically important differences between the timing regimens of inhaling hypertonic saline before, during or after airway clearance techniques in the mean amount of improvement in lung function or symptom scores (77 participants), with the between-group comparisons being non-significant (low-certainty evidence). While there may be little or no difference in the rating of satisfaction when hypertonic saline was inhaled before versus during the airway clearance techniques (64 participants) (with the 95% confidence interval including the possibility of both a higher and lower rating of satisfaction), satisfaction may be lower on a 100-mm scale when inhaled after the airway clearance techniques compared to before: mean difference (MD) 20.38 mm (95% confidence interval (CI) 12.10 to 28.66) and when compared to during the techniques, MD 14.80 mm (95% CI 5.70 to 23.90). Perceived effectiveness showed similar results: little or no difference for inhalation before versus during airway clearance techniques (64 participants); may be lower when inhaled after the airway clearance techniques compared to before, MD 10.62 (95% CI 2.54 to 18.70); and also when compared to during the techniques, MD 15.60 (95% CI 7.55 to 23.65). There were no quality of life or adverse events reported in any of the trials. AUTHORS' CONCLUSIONS: Timing of hypertonic saline inhalation makes little or no difference to lung function (low-certainty evidence). However, inhaling hypertonic saline before or during airway clearance techniques may maximise perceived efficacy and satisfaction. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available. The identified trials were all of very short intervention periods, so longer-term research could be conducted to establish the effects arising from regular use, which would incorporate the influence of changes in adherence with long-term use, as well as generating data on any adverse effects that occur with long-term use.

Analysis of reporting completeness in exercise cancer trials: a systematic review.

BACKGROUND: Exercise is an effective therapeutic intervention for cancer survivors. Concerns about the completeness of reporting of exercise interventions have been raised in the literature, but without any formal analysis. This study aimed to evaluate the completeness of reporting of exercise interventions for cancer survivors in a large sample of randomized clinical trials (RCTs). METHODS: We developed a pre-defined protocol. We searched MEDLINE, EMBASE, and CENTRAL for exercise trials in oncology between 2010 and 2017. Pairs of independent researchers screened the records, extracted study characteristics, and assessed 16 items on the TIDieR checklist (i.e., the 12 items, with item 5 divided into two and item 8 divided into four). For each of these items, the percentage of interventions in the included studies that reported the item was calculated. RESULTS: We included 131 RCTs reporting 138 interventions in the analysis. Breast cancer was the most common type of cancer (69, 50%), and aerobic exercise was the most studied exercise modality (43, 30%) followed by combined aerobic and resistance training (40, 28%). Completeness of reporting ranged from 42 to 96% among the TIDieR items; none of the items was fully reported. 'Intervention length' was the most reported item across interventions (133, 96%), followed by 'rationale' (131, 95%), whereas 'provider' (58, 42%) and 'how well (planned)' (63, 46%) were the two least reported items. Half of the TIDieR items were completely reported in 50 to 70% of the interventions, and only four items were reported in more than 80% of the interventions (Items 2 and 8a to c). The seven items deemed to be core for replication (Items 3 to 9) exhibited a mean reporting of 71%, ranging from 42 to 96%. CONCLUSION: Exercise training interventions for cancer survivors are incompletely reported across RCTs published between 2010 and 2017. The reporting of information about the provider, materials, and modifications require urgent improvements. Stronger reporting will enhance usability of trial reports by both healthcare providers and survivors, and will help to reduce research waste.

Side lying during nebulisation can significantly improve apical deposition in healthy adults and adults with mild cystic fibrosis lung disease: a randomised crossover trial.

BACKGROUND: In people with and without Cystic Fibrosis (CF), does side lying during nebulisation change: the proportion of the dose loaded in the nebuliser that is deposited in the lungs; the uniformity of deposition throughout the lungs; or the apical drug density as a percentage of the drug density in the remaining lung? Do these effects differ depending on the degree of lung disease present? METHODS: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors, involving 39 adults: 13 healthy, 13 with mild CF lung disease (FEV1 > 80%pred), and 13 with more advanced CF lung disease (FEV1 < 80%pred). In random order, 4 mL of nebulised radioaerosol was inhaled in upright sitting and in alternate right and left side lying at 2-min intervals, for 20 min. RESULTS: Compared to sitting upright, lung deposition and the uniformity of deposition were not significantly altered by side lying in any of the three groups. In sitting, the density of the deposition was significantly less in the apical regions than in the rest of the lung in all participants. Side lying significantly improved apical deposition in healthy adults (MD, 13%; 95% CI, 7 to 19), and in minimal CF lung disease (MD, 4%; 95% CI, 1 to 7) but not in advanced disease (MD, 4%; 95% CI, - 2 to 9). CONCLUSION: Alternating between right and left side lying during nebulisation significantly improves apical deposition in healthy adults and in adults with mild CF lung disease, without substantial detriment to overall deposition. TRIAL REGISTRATION: ACTRN12611000674932 (Healthy), ACTRN12611000672954 (CF) Retrospectively registered 4/7/2011.

Nasal High Flow for Stable Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

There is a growing body of evidence supporting the use of nasal high flow (NHF) to treat acute respiratory failure, particularly in Chronic Obstructive Pulmonary Disease (COPD) patients. Conversely, there are sparse data evaluating its effects in stable COPD patients.We identified randomized controlled trial comparing the effects of delivering air or oxygen via NHF, compared with delivering the same gas without NHF, in stable COPD patients through a systematic search using MEDLINE, CENTRAL, Science Direct, and others sources until January 2019. Study selection, data extraction and assessment of the risk of bias (using the Cochrane Risk of Bias tool) was performed by two independent authors.We included 6 studies (339 participants). Our meta-analysis showed a significant reduction of arterial carbon dioxide pressure (PaCO2) at long (two studies, MD -3 mmHg, [95% Confidence interval (CI) -4 to -2]) and short-term (two studies, MD -3 mmHg [95% CI -4 to -2]). NHF significantly improved quality of life on the St George's Respiratory Questionnaire (two studies, MD -5 out of 100, [95% CI -8 to -2]). NHF significantly reduced the rate of acute exacerbation at 1 year (one study, rate ratio: 0.6, [95% CI 0.6 to 0.7]). NHF did not significantly improve exercise capacity, hospitalization rate or mortality, but improved breathing pattern.NHF reduced PaCO2, acute exacerbation and improved quality of life in stable COPD patients. Further long-term studies are needed to confirm the present results and provide more data on patient-centered outcome such as quality of life, exacerbation, hospitalization and mortality.

Characteristics of patient communication and prevalence of communication difficulty in the intensive care unit: An observational study.

PURPOSE: To summarise the patient communication status in an intensive care unit (ICU), including methods of communication used and the frequency, degree and nature of communication breakdown. MATERIALS AND METHODS: A multidisciplinary daily ward audit was conducted on ten consecutive weekdays in a 30-bed general ICU of a tertiary Australian hospital. Data included patient demographics, patients' mode of communication and the level of difficulty in communicating. Descriptive statistics and means (standard deviation)/medians (interquartile range) were used to summarise the data. RESULTS: Over the audit period, data were collected from 87 patients (median age 58 years, interquartile range 43 to 67; 60% males), equivalent to 232 occupied bed days. Patients from non-English-speaking backgrounds accounted for 14% of the cohort, with Mandarin the most common non-English language. Altered cognition occurred on 11% of bed days. Staff reported difficulty in communicating with patients on 35% of bed days, with an inability to communicate with patients in 49% of these cases. Alternate modes of communication were reported, with gesture the most common, but they were not used with all suitable patients. CONCLUSIONS: About one-third of the caseload in the ICU experienced difficulty in communicating. While alternate communication methods were reported, they were not used with all patients. A multidisciplinary approach to enhance communication ability may be beneficial.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis. SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings.Date of the most recent search: 06 June 2018. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. MAIN RESULTS: We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence). AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

The use of an alternate side lying positioning strategy during inhalation therapy does not prolong nebulisation time in adults with Cystic Fibrosis: a randomised crossover trial.

BACKGROUND: Inhalation of nebulised medications is performed in upright sitting to maximise lung volumes. The pattern of deposition is poor for inhaled medications in people with Cystic Fibrosis. The pattern tends to be non-uniform and typically the upper lobes receive a reduced dose compared to the rest of the lung. One strategy that has been proposed as having the potential to improve homogeneity of deposition is to adopt an alternate side lying position for the inhalation procedure. This study sought to determine whether, among adults with Cystic Fibrosis, there is any disadvantage to delivery time of nebulised medications with a strategy of alternate side lying, compared to upright sitting. METHODS: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors was undertaken. The participants were 24 adults with stable Cystic Fibrosis. They inhaled 4 mL of normal saline via an LC Star™ nebuliser twice within 24 h. In random order, participants sat upright throughout nebulisation, or alternated between left and right side lying at each minute during the nebulisation period. The nebuliser was stopped and weighed each minute until the residual volume was reached. The primary outcome was the time required for 3.5 mL to be delivered. The secondary outcomes were: respiratory rate; ratio of the volume delivered on right and left sides; and calculation of how long the periods in side lying can be extended without causing greater than 20% discrepancy in dose delivered in the two positions. RESULTS: The delivery time did not significantly differ between sitting and side lying (mean difference 0.58 min, 95% confidence interval (CI) -1.40 to 0.24). There was no significant correlation between delivery time, lung function or subject height (all R2 < 0.4). Increasing side lying duration from 1 to 2 min did not significantly impact the dose delivered on each side. Turning each 3 min however, significantly worsened the disparity (mean ratio 1.32, 95% CI 1.24 to 1.40). CONCLUSION: Side lying during inhalation therapy does not prolong nebulisation time. 2-min periods should provide an equal dose in the two side lying positions. TRIAL REGISTRATION: Prospectively registered on 4 July 2011; ACTRN12611000672954 .

Citation of prior research has increased in introduction and discussion sections with time: A survey of clinical trials in physiotherapy.

BACKGROUND/AIMS: Many clinical trials are reported without reference to the existing relevant high-quality research. This study aimed to investigate the extent to which authors of reports of clinical trials of physiotherapy interventions try to use high-quality clinical research to (1) help justify the need for the trial in the introduction and (2) help interpret the trial's results in the discussion. METHODS: Data were extracted from 221 clinical trials that were randomly selected from the Physiotherapy Evidence Database: 70 published in 2001 (10% sample) and 151 published in 2015 (10% sample). The Physiotherapy Evidence Database score (which rates methodological quality and completeness of reporting) for each trial was also downloaded. RESULTS: Overall 41% of trial reports cited a systematic review or the results of a search for other evidence in the introduction section: 20% for 2001 and 50% for 2015 (relative risk = 2.3, 95% confidence interval = 1.5-3.8). For the discussion section, only 1 of 221 trials integrated the results of the trial into an existing meta-analysis, but citation of a relevant systematic review did increase from 17% in 2001 to 34% in 2015. There was no relationship between citation of existing research and the total Physiotherapy Evidence Database score. CONCLUSION: Published reports of clinical trials of physiotherapy interventions increasingly cite a systematic review or the results of a search for other evidence in the introduction, but integration with existing research in the discussion section is very rare. To encourage the use of existing research, stronger recommendations to refer to existing systematic reviews (where available) could be incorporated into reporting checklists and journal editorial guidelines.

A randomised trial of hypertonic saline during hospitalisation for exacerbation of cystic fibrosis.

BACKGROUND: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF). OBJECTIVES: To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation. METHODS: 132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay. RESULTS: All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ. CONCLUSIONS: Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution. TRIAL REGISTRATION NUMBER: ACTRN12605000780651.

Return of Voice for Ventilated Tracheostomy Patients in ICU: A Randomized Controlled Trial of Early-Targeted Intervention.

OBJECTIVES: A cuffed tracheostomy tube facilitates prolonged mechanical ventilation and weaning but usually leads to prolonged voicelessness, which can be one of the most negative experiences of hospitalization. No randomized trials have examined the effects of targeted early communication intervention for the restoration of voice in ventilated tracheostomy patients in the ICU. DESIGN: A prospective randomized clinical trial. SETTING: The trial was conducted in the ICU of an urban tertiary level hospital. PATIENTS: Thirty adult participants enrolled, with 15 randomly allocated to the intervention and control groups. INTERVENTIONS: The early intervention group received early cuff deflation and insertion of an in-line speaking valve during mechanical ventilation. The control group received standard cuff deflation and a speaking valve during self-ventilation. A speech-language pathologist provided all treatments. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was time from tracheostomy insertion to phonation. Early intervention significantly hastened return to phonation (median difference = 11 d; hazard ratio = 3.66; 95% CI, 1.54-8.68) with no significant effect on duration of tracheostomy cannulation (hazard ratio = 1.40; 95% CI, 0.65-3.03), duration of mechanical ventilation in days from tracheostomy insertion (hazard ratio = 1.19; 95% CI, 0.58-2.51), length of stay in ICU (hazard ratio = 1.16; 95% CI, 0.54-2.52), or time to return to oral intake (hazard ratio = 2.35; 95% CI, 0.79-6.98). Adverse events were low and equal in both groups. There was no significant change in measures of quality of life. CONCLUSIONS: Focused early intervention for communication during mechanical ventilation allows the restoration of phonation significantly sooner than standard treatment, with no increase in complications in a small patient cohort. Although these results are favorable, further research is needed to determine whether the effects on any of the secondary outcomes are statistically significant and clinically important.

Timing of dornase alfa inhalation for cystic fibrosis.

BACKGROUND: Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. OBJECTIVES: To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). SEARCH METHODS: Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. SELECTION CRITERIA: Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. MAIN RESULTS: We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. AUTHORS' CONCLUSIONS: The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Timing of hypertonic saline inhalation for cystic fibrosis.

BACKGROUND: Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. OBJECTIVES: To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. SEARCH METHODS: We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 19 December 2016. SELECTION CRITERIA: Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. DATA COLLECTION AND ANALYSIS: Both authors independently assessed the trials identified by the search for potential inclusion in the review. MAIN RESULTS: The searches identified 97 trial reports which represented 46 studies, of which two studies (providing data on 63 participants) met our inclusion criteria. Both studies used a cross-over design. Both studies had low risk of all types of bias except the participants and the therapists who applied the treatments were not blinded. Intervention periods ranged from one treatment to three treatments in one day. The effects of the various regimens on lung function were non-significant. Satisfaction was rated significantly lower on a 100-mm scale when hypertonic saline was inhaled after the airway clearance techniques: mean differences 20.38 mm (95% confidence interval 12.10 to 28.66) compared to before airway clearance techniques and 14.80 mm (95% confidence interval 5.70 to 23.90) compared to during the techniques. Perceived effectiveness showed similar significant results. Other outcomes were unaffected by the timing regimen used. No trials compared morning versus evening inhalation of hypertonic saline. AUTHORS' CONCLUSIONS: People with cystic fibrosis could be encouraged to inhale hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction, even though these timing regimens may not have any better effect on lung function than inhalation after airway clearance techniques. Given the long-term efficacy of hypertonic saline has only been established for twice-daily inhalations, clinicians should advise patients to inhale hypertonic saline twice daily. However, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available.

Postoperative outcomes following preoperative inspiratory muscle training in patients undergoing cardiothoracic or upper abdominal surgery: a systematic review and meta analysis.

OBJECTIVE: To evaluate whether preoperative inspiratory muscle training is effective in preventing postoperative pulmonary complications and reducing length of hospital stay in people undergoing cardiothoracic or upper abdominal surgery. DATA SOURCES: Medline, CINAHL, AMED, PsychINFO, Scopus, PEDro, and the Cochrane Library. REVIEW METHODS: A systematic review and meta analysis of randomized controlled trials (or quasi-randomized controlled trials) investigating a form of preoperative inspiratory muscle training, compared with sham or no inspiratory muscle training. Participants were adults (16 years and over) awaiting elective open cardiac, thoracic, or upper abdominal surgery. Methodological quality was assessed using the PEDro scale. RESULTS: Eight studies involving 295 participants were eligible for inclusion. The trained group had significantly higher maximal inspiratory pressure at the end of the preoperative training period (mean difference: 15 cm H2O, 95% confidence interval (CI): 9 to 21). This benefit was maintained through the early postoperative period, when lung function also recovered significantly more quickly in the trained group. Inspiratory muscle training also substantially reduced postoperative pulmonary complications (relative risk 0.48, 95% CI 0.26 to 0.89). Although not statistically significant, length of hospital stay also tended to favour the trained group. There were no statistically significant differences between the groups for the remaining outcomes. Participant satisfaction with inspiratory muscle training was high. CONCLUSION: Preoperative inspiratory muscle training significantly improves respiratory (muscle) function in the early postoperative period, halving the risk of pulmonary complications. The training does not increase length of stay, but more data are required to confirm whether it reduces length of stay.

Reporting of confidence intervals, achievement of intended sample size, and adjustment for multiple primary outcomes in randomised trials of physical therapy interventions: an analysis of 100 representatively sampled trials.

BACKGROUND: The physical therapy profession has made efforts to increase the use of confidence intervals due to the valuable information they provide for clinical decision-making. Confidence intervals indicate the precision of the results and describe the strength and direction of a treatment effect measure. OBJECTIVES: To determine the prevalence of reporting of confidence intervals, achievement of intended sample size, and adjustment for multiple primary outcomes in randomised trials of physical therapy interventions. METHODS: We randomly selected 100 trials published in 2021 and indexed on the Physiotherapy Evidence Database. Two independent reviewers extracted the number of participants, any sample size calculation, and any adjustments for multiple primary outcomes. We extracted whether at least one between-group comparison was reported with a 95 % confidence interval and whether any confidence intervals were interpreted. RESULTS: The prevalence of use of confidence intervals was 47 % (95 % CI 38, 57). Only 6 % of trials (95 % CI: 3, 12) both reported and interpreted a confidence interval. Among the 100 trials, 59 (95 % CI: 49, 68) calculated and achieved the required sample size. Among the 100 trials, 19 % (95 % CI: 13, 28) had a problem with unadjusted multiplicity on the primary outcomes. CONCLUSIONS: Around half of trials of physical therapy interventions published in 2021 reported confidence intervals around between-group differences. This represents an increase of 5 % from five years earlier. Very few trials interpreted the confidence intervals. Most trials reported a sample size calculation, and among these most achieved that sample size. There is still a need to increase the use of adjustment for multiple comparisons.

Preoperative respiratory muscle training reduces the risk of pulmonary complications and the length of hospital stay after cardiac surgery: a systematic review.

QUESTIONS: What is the effect of preoperative respiratory muscle training (RMT) on the incidence of postoperative pulmonary complications (PPCs) after open cardiac surgery? What is the effect of RMT on the duration of mechanical ventilation, postoperative length of stay and respiratory muscle strength? DESIGN: Systematic review of randomised trials with meta-analysis. PARTICIPANTS: Adults undergoing elective open cardiac surgery. INTERVENTION: The experimental groups received preoperative RMT and the comparison groups received no intervention. OUTCOME MEASURES: The primary outcomes were PPCs, length of hospital stay, respiratory muscle strength, oxygenation and duration of mechanical ventilation. The methodological quality of studies was assessed using the PEDro scale and the overall certainty of the evidence was assessed using the GRADE approach. RESULTS: Eight trials involving 696 participants were included. Compared with the control group, the respiratory training group had fewer PPCs (RR 0.51, 95% CI 0.38 to 0.70), less pneumonia (RR 0.44, 95% CI 0.25 to 0.78), shorter hospital stay (MD -1.7 days, 95% CI -2.4 to -1.1) and higher maximal inspiratory pressure values at the end of the training protocol (MD 12 cmH2O, 95% CI 8 to 16). The mechanical ventilation time was similar in both groups. The quality of evidence was high for pneumonia, length of hospital stay and maximal inspiratory pressure. CONCLUSION: Preoperative RMT reduced the risk of PPCs and pneumonia after cardiac surgery. The training also improved the maximal inspiratory pressure and reduced hospital stay. The effects on PPCs were large enough to warrant use of RMT in this population. REGISTRATION: CRD42021227779.