How well do orthodontic RCTs comply with CONSORT guidelines?

OBJECTIVES: To assess the changes in compliance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized controlled trials (RCTs) in four orthodontic journals. To assess whether reporting of randomization, concealment, and blinding has improved. METHODS: Electronic hand searching was undertaken to identify orthodontic RCTs published in four orthodontic journals from January 2016 to June 2017 (T1) and from January 2019 to June 2020 (T2). The journals were the American Journal of Orthodontics and Dentofacial Orthopaedics (AJO-DO), Angle Orthodontist (AO), European Journal of Orthodontics (EJO), and Journal of Orthodontics (JO). Each item on the CONSORT checklist was scored as either reported, not reported, or not applicable for each paper reporting an RCT. RESULTS: The study included 69 papers reporting an RCT published in T1 and 64 RCTs published in T2. The median CONSORT score in T1 was 48.7% (interquartile range [IQR] 27.6%, 68.6%) and 67% in T2 (IQR 43.9%, 79.5%). This increase was statistically significant (P = 0.001) and largely attributable to improved reporting in AO (P = 0.016) and EJO (P = 0.023). Reporting did not change significantly in AJO-DO (P = 0.13) or in JO (P = 1.0). Reporting of random allocation sequence generation (OR 2.09; 95% CI 1.01, 4.29) and concealment of allocation (OR 2.27%, 95% CI 1.12, 4.57) were significantly higher in T2 compared with T1. Reporting of blinding did not change significantly. CONCLUSION: Overall reporting of CONSORT items in reports of orthodontic RCTs published in the AJO-DO, AO, EJO, and JO, improved significantly from 2016-17 to 2019-20. This could be improved further by authors, journal referees, and editors adhering to the guidelines.

Intermittent prophylactic antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a common but under-diagnosed chronic disorder characterised by permanent dilation of the airways arising from a cycle of recurrent infection and inflammation. Symptoms including chronic, persistent cough and productive phlegm are a significant burden for people with bronchiectasis, and the main aim of treatment is to reduce exacerbation frequency and improve quality of life. Prophylactic antibiotic therapy aims to break this infection cycle and is recommended by clinical guidelines for adults with three or more exacerbations a year, based on limited evidence. It is important to weigh the evidence for bacterial suppression against the prevention of antibiotic resistance and further evidence is required on the safety and efficacy of different regimens of intermittently administered antibiotic treatments for people with bronchiectasis. OBJECTIVES: To evaluate the safety and efficacy of intermittent prophylactic antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted searches on 6 September 2021, with no restriction on language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least three months' duration comparing an intermittent regime of prophylactic antibiotics with placebo, usual care or an alternate intermittent regimen. Intermittent prophylactic administration was defined as repeated courses of antibiotics with on-treatment and off-treatment intervals of at least 14 days' duration. We included adults and children with a clinical diagnosis of bronchiectasis confirmed by high resolution computed tomography (HRCT), plain film chest radiograph, or bronchography and a documented history of recurrent chest infections. We excluded studies where participants received high dose antibiotics immediately prior to enrolment or those with a diagnosis of cystic fibrosis, allergic bronchopulmonary aspergillosis (ABPA), primary ciliary dyskinesia, hypogammaglobulinaemia, sarcoidosis, or a primary diagnosis of COPD. Our primary outcomes were exacerbation frequency and serious adverse events. We did not exclude studies on the basis of review outcomes. DATA COLLECTION AND ANALYSIS: We analysed dichotomous data as odds ratios (ORs) or relative risk (RRs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures expected by Cochrane. We conducted GRADE assessments for the following primary outcomes: exacerbation frequency; serious adverse events and secondary outcomes: antibiotic resistance; hospital admissions; health-related quality of life. MAIN RESULTS: We included eight RCTs, with interventions ranging from 16 to 48 weeks, involving 2180 adults. All evaluated one of three types of antibiotics over two to six cycles of 28 days on/off treatment: aminoglycosides, ß-lactams or fluoroquinolones. Two studies also included 12 cycles of 14 days on/off treatment with fluoroquinolones. Participants had a mean age of 63.6 years, 65% were women and approximately 85% Caucasian. Baseline FEV1 ranged from 55.5% to 62.6% predicted. None of the studies included children. Generally, there was a low risk of bias in the included studies. Antibiotic versus placebo: cycle of 14 days on/off. Ciprofloxacin reduced the frequency of exacerbations compared to placebo (RR 0.75, 95% CI 0.61 to 0.93; I2 = 65%; 2 studies, 469 participants; moderate-certainty evidence), with eight people (95% CI 6 to 28) needed to treat for an additional beneficial outcome. The intervention increased the risk of antibiotic resistance more than twofold (OR 2.14, 95% CI 1.36 to 3.35; I2 = 0%; 2 studies, 624 participants; high-certainty evidence). Serious adverse events, lung function (FEV1), health-related quality of life, and adverse effects did not differ between groups. Antibiotic versus placebo: cycle of 28 days on/off. Antibiotics did not reduce overall exacerbation frequency (RR 0.92, 95% CI 0.82 to 1.02; I2 = 0%; 8 studies, 1695 participants; high-certainty evidence) but there were fewer severe exacerbations (OR 0.59, 95% CI 0.37 to 0.93; I2 = 54%; 3 studies, 624 participants), though this should be interpreted with caution due to low event rates. The risk of antibiotic resistance was more than twofold higher based on a pooled analysis (OR 2.20, 95% CI 1.42 to 3.42; I2 = 0%; 3 studies, 685 participants; high-certainty evidence) and consistent with unpooled data from four further studies. Serious adverse events, time to first exacerbation, duration of exacerbation, respiratory-related hospital admissions, lung function, health-related quality of life and adverse effects did not differ between study groups. Antibiotic versus usual care. We did not find any studies that compared intermittent antibiotic regimens with usual care. Cycle of 14 days on/off versus cycle of 28 days on/off. Exacerbation frequency did not differ between the two treatment regimens (RR 1.02, 95% CI 0.84 to 1.24; I2 = 71%; 2 studies, 625 participants; moderate-certainty evidence) However, inconsistencies in the results from the two trials in this comparison indicate that the apparent aggregated similarities may not be reliable. There was no evidence of a difference in antibiotic resistance between groups (OR 1.00, 95% CI 0.68 to 1.48; I2 = 60%; 2 studies, 624 participants; moderate-certainty evidence). Serious adverse events, adverse effects, lung function and health-related quality of life did not differ between the two antibiotic regimens. AUTHORS' CONCLUSIONS: Overall, in adults who have frequent chest infections, long-term antibiotics given at 14-day on/off intervals slightly reduces the frequency of those infections and increases antibiotic resistance. Intermittent antibiotic regimens result in little to no difference in serious adverse events. The impact of intermittent antibiotic therapy on children with bronchiectasis is unknown due to an absence of evidence, and further research is needed to establish the potential risks and benefits.

Running shoes for preventing lower limb running injuries in adults.

BACKGROUND: Lower-limb running injuries are common. Running shoes have been proposed as one means of reducing injury risk. However, there is uncertainty as to how effective running shoes are for the prevention of injury. It is also unclear how the effects of different characteristics of running shoes prevent injury. OBJECTIVES: To assess the effects (benefits and harms) of running shoes for preventing lower-limb running injuries in adult runners. SEARCH METHODS: We searched the following databases: CENTRAL, MEDLINE, Embase, AMED, CINAHL Plus and SPORTDiscus plus trial registers WHO ICTRP and ClinicalTrials.gov. We also searched additional sources for published and unpublished trials. The date of the search was June 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs involving runners or military personnel in basic training that either compared a) a running shoe with a non-running shoe; b) different types of running shoes (minimalist, neutral/cushioned, motion control, stability, soft midsole, hard midsole); or c) footwear recommended and selected on foot posture versus footwear not recommended and not selected on foot posture for preventing lower-limb running injuries. Our primary outcomes were number of people sustaining a lower-limb running injury and number of lower-limb running injuries. Our secondary outcomes were number of runners who failed to return to running or their previous level of running, runner satisfaction with footwear, adverse events other than musculoskeletal injuries, and number of runners requiring hospital admission or surgery, or both, for musculoskeletal injury or adverse event. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and performed data extraction and risk of bias assessment. The certainty of the included evidence was assessed using GRADE methodology. MAIN RESULTS: We included 12 trials in the analysis which included a total of 11,240 participants, in trials that lasted from 6 to 26 weeks and were carried out in North America, Europe, Australia and South Africa. Most of the evidence was low or very low certainty as it was not possible to blind runners to their allocated running shoe, there was variation in the definition of an injury and characteristics of footwear, and there were too few studies for most comparisons. We did not find any trials that compared running shoes with non-running shoes. Neutral/cushioned versus minimalist (5 studies, 766 participants) Neutral/cushioned shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with minimalist shoes (low-certainty evidence) (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.59 to 1.01). One trial reported that 67% and 92% of runners were satisfied with their neutral/cushioned or minimalist running shoes, respectively (RR 0.73, 95% CI 0.47 to 1.12). Another trial reported mean satisfaction scores ranged from 4.0 to 4.3 in the neutral/ cushioned group and 3.6 to 3.9 in the minimalist running shoe group out of a total of 5. Hence neutral/cushioned running shoes may make little or no difference to runner satisfaction with footwear (low-certainty evidence). Motion control versus neutral / cushioned (2 studies, 421 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral / cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.92, 95% CI 0.30 to 2.81). Soft midsole versus hard midsole (2 studies, 1095 participants) Soft midsole shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with hard midsole shoes (low-certainty of evidence) (RR 0.82, 95% CI 0.61 to 1.10). Stability versus neutral / cushioned (1 study, 57 participants) It is uncertain whether or not stability shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral/cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.49, 95% CI 0.18 to 1.31). Motion control versus stability (1 study, 56 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with stability shoes because the quality of the evidence has been assessed as very low certainty (RR 3.47, 95% CI 1.43 to 8.40). Running shoes prescribed and selected on foot posture (3 studies, 7203 participants) There was no evidence that running shoes prescribed based on static foot posture reduced the number of injuries compared with those who received a shoe not prescribed based on foot posture in military recruits (Rate Ratio 1.03, 95% CI 0.94 to 1.13). Subgroup analysis confirmed these findings were consistent between males and females. Therefore, prescribing running shoes and selecting on foot posture probably makes little or no difference to lower-limb running injuries (moderate-certainty evidence). Data were not available for all other review outcomes. AUTHORS' CONCLUSIONS: Most evidence demonstrates no reduction in lower-limb running injuries in adults when comparing different types of running shoes. Overall, the certainty of the evidence determining whether different types of running shoes influence running injury rates was very low to low, and as such we are uncertain as to the true effects of different types of running shoes upon injury rates. There is no evidence that prescribing footwear based on foot type reduces running-related lower-limb injures in adults. The evidence for this comparison was rated as moderate and as such we can have more certainty when interpreting these findings. However, all three trials included in this comparison used military populations and as such the findings may differ in recreational runners.  Future researchers should develop a consensus definition of running shoe design to help standardise classification. The definition of a running injury should also be used consistently and confirmed via health practitioners. More researchers should consider a RCT design to increase the evidence in this area. Lastly, future work should look to explore the influence of different types or running shoes upon injury rates in specific subgroups.

Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial.

BACKGROUND: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. METHODS: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. FINDINGS: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). INTERPRETATION: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Occupational therapy delivered by specialists versus non-specialists for people with schizophrenia.

BACKGROUND: Schizophrenia is a severe mental health condition that is characterised by positive symptoms, such as hallucinations and delusions; negative symptoms, such as flattened affect, thought disorder (disrupted speech), and lack of motivation; and cognitive symptoms, such as problems with memory and attention. Schizophrenia can occur as an isolated episode, or as a recurring cycle of remission and relapse, and is associated with impairment in psychosocial and occupational functioning.Although antipsychotic drugs are the main treatment for people with schizophrenia, in most countries mental health services usually provide a range of add-on interventions, including occupational therapy. This is a complex intervention designed to support and enable continued participation in daily life through engagement in activities and occupations meaningful to the individual. Occupational therapists are professionals trained to deliver therapy where the emphasis is on improving occupational function and participation rather than treating symptoms, and uses a wide range of methods based on the needs of individuals. However, similar interventions may also be delivered by staff not trained as occupational therapists. OBJECTIVES: To examine the effects of occupational therapy delivered by occupational therapists compared to occupational therapy delivered by any other person for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers) on 4 November 2016 and 26 July 2018. SELECTION CRITERIA: All randomised controlled trials evaluating the functional or clinical outcomes of occupational therapy, or both, for people with schizophrenia delivered by occupational therapists compared with occupational therapy for people with schizophrenia delivered by anyone other than occupational therapists. DATA COLLECTION AND ANALYSIS: Review authors independently inspected citations, selected studies, extracted data, and appraised study quality. MAIN RESULTS: The search yielded 1633 records. Of these, we retrieved 17 full-text reports (14 studies) for further scrutiny, which we subsequently excluded as they did not meet our inclusion criteria. AUTHORS' CONCLUSIONS: Currently there are no randomised controlled trials comparing delivery of occupational therapy for people diagnosed with schizophrenia by occupational therapists with delivery of similar interventions by anyone other than occupational therapists. Research studies employing methodologically robust trial designs are needed to establish whether or not there are better outcomes for people with a diagnosis of schizophrenia with occupational therapy that is delivered by trained occupational therapists.

De-escalation techniques for managing non-psychosis induced aggression in adults.

BACKGROUND: Aggression occurs frequently within health and social care settings. It can result in injury to patients and staff and can adversely affect staff performance and well-being. De-escalation is a widely used and recommended intervention for managing aggression, but the efficacy of the intervention as a whole and the specific techniques that comprise it are unclear. OBJECTIVES: To assess the effects of de-escalation techniques for managing non-psychosis-induced aggression in adults in care settings, in both staff and service users. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and 14 other databases in September 2017, plus three trials registers in October 2017. We also checked references, and contacted study authors and authorities in the field to identify additional published and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing de-escalation techniques with standard practice or alternative techniques for managing aggressive behaviour in adult care settings. We excluded studies in which participants had psychosis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: This review includes just one cluster-randomised study of 306 older people with dementia and an average age of 86 years, conducted across 16 nursing homes in France. The study did not measure any of our primary or secondary outcomes but did measure behavioural change using three measurement scales: the Cohen-Mansfield Agitation Inventory (CMAI; 29-item scale), the Neuropsychiatric Inventory (NPI; 12-item scale), and the Observation Scale (OS; 25-item scale). For the CMAI, the study reports a Global score (29 items rated on a seven-point scale (1 = never occurs to 7 = occurs several times an hour) and summed to give a total score ranging from 29 to 203) and mean scores (evaluable items (rated on the same 7-point scale) divided by the theoretical total number of items) for the following four domains: Physically Non-Aggressive Behaviour, such as pacing (13 items); Verbally Non-Aggressive Behaviour, such as repetition (four items); Physically Aggressive Behaviour, such as hitting (nine items); and Verbally Aggressive Behaviour, such as swearing (three items). Four of the five CMAI scales improved in the intervention group (Global: change mean difference (MD) -5.69 points, 95% confidence interval (CI) -9.59 to -1.79; Physically Non-Aggressive: change MD -0.32 points, 95% CI -0.49 to -0.15; Verbally Non-Aggressive: change MD -0.44 points, 95% CI -0.69 to -0.19; and Verbally Aggressive: change MD -0.16 points, 95% CI -0.31 to -0.01). There was no difference in change scores on the Physically Aggressive scale (MD -0.08 points, 95% CI -0.37 to 0.21). Using GRADE guidelines, we rated the quality of this evidence as very low due to high risk of bias and indirectness of the outcome measures. There were no differences in NPI or OS change scores between groups by the end of the study.We also identified one ongoing study. AUTHORS' CONCLUSIONS: The limited evidence means that uncertainty remains around the effectiveness of de-escalation and the relative efficacy of different techniques. High-quality research on the effectiveness of this intervention is therefore urgently needed.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Head-to-head trials of antibiotics for bronchiectasis.

BACKGROUND: The diagnosis of bronchiectasis is defined by abnormal dilation of the airways related to a pathological mechanism of progressive airway destruction that is due to a 'vicious cycle' of recurrent bacterial infection, inflammatory mediator release, airway damage, and subsequent further infection. Antibiotics are the main treatment option for reducing bacterial burden in people with exacerbations of bronchiectasis and for longer-term eradication, but their use is tempered against potential adverse effects and concerns regarding antibiotic resistance. The comparative effectiveness, cost-effectiveness, and safety of different antibiotics have been highlighted as important issues, but currently little evidence is available to help resolve uncertainty on these questions. OBJECTIVES: To evaluate the comparative effects of different antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified randomised controlled trials (RCTs) through searches of the Cochrane Airways Group Register of trials and online trials registries, run 30 April 2018. We augmented these with searches of the reference lists of published studies. SELECTION CRITERIA: We included RCTs reported as full-text articles, those published as abstracts only, and unpublished data. We included adults and children (younger than 18 years) with a diagnosis of bronchiectasis by bronchography or high-resolution computed tomography who reported daily signs and symptoms, such as cough, sputum production, or haemoptysis, and those with recurrent episodes of chest infection; we included studies that compared one antibiotic versus another when they were administered by the same delivery method. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial selection, data extraction, and risk of bias. We assessed overall quality of the evidence using GRADE criteria. We made efforts to collect missing data from trial authors. We have presented results with their 95% confidence intervals (CIs) as mean differences (MDs) or odds ratios (ORs). MAIN RESULTS: Four randomised trials were eligible for inclusion in this systematic review - two studies with 83 adults comparing fluoroquinolones with ß-lactams and two studies with 55 adults comparing aminoglycosides with polymyxins.None of the included studies reported information on exacerbations - one of our primary outcomes. Included studies reported no serious adverse events - another of our primary outcomes - and no deaths. We graded this evidence as low or very low quality. Included studies did not report quality of life. Comparison between fluoroquinolones and ß-lactams (amoxicillin) showed fewer treatment failures in the fluoroquinolone group than in the amoxicillin group (OR 0.07, 95% CI 0.01 to 0.32; low-quality evidence) after 7 to 10 days of therapy. Researchers reported that Pseudomonas aeruginosa infection was eradicated in more participants treated with fluoroquinolones (Peto OR 20.09, 95% CI 2.83 to 142.59; low-quality evidence) but provided no evidence of differences in the numbers of participants showing improvement in sputum purulence (OR 2.35, 95% CI 0.96 to 5.72; very low-quality evidence). Study authors presented no evidence of benefit in relation to forced expiratory volume in one second (FEV1). The two studies that compared polymyxins versus aminoglycosides described no clear differences between groups in the proportion of participants with P aeruginosa eradication (OR 1.40. 95% CI 0.36 to 5.35; very low-quality evidence) or improvement in sputum purulence (OR 0.16, 95% CI 0.01 to 3.85; very low-quality evidence). The evidence for changes in FEV1 was inconclusive. Two of three trials reported adverse events but did not report the proportion of participants experiencing one or more adverse events, so we were unable to interpret the information. AUTHORS' CONCLUSIONS: Limited low-quality evidence favours short-term oral fluoroquinolones over beta-lactam antibiotics for patients hospitalised with exacerbations. Very low-quality evidence suggests no benefit from inhaled aminoglycosides verus polymyxins. RCTs have presented no evidence comparing other modes of delivery for each of these comparisons, and no RCTs have included children. Overall, current evidence from a limited number of head-to-head trials in adults or children with bronchiectasis is insufficient to guide the selection of antibiotics for short-term or long-term therapy. More research on this topic is needed.

Self-management for bronchiectasis.

BACKGROUND: Bronchiectasis is a long term respiratory condition with an increasing rate of diagnosis. It is associated with persistent symptoms, repeated infective exacerbations, and reduced quality of life, imposing a burden on individuals and healthcare systems. The main aims of therapeutic management are to reduce exacerbations and improve quality of life. Self-management interventions are potentially important for empowering people with bronchiectasis to manage their condition more effectively and to seek care in a timely manner. Self-management interventions are beneficial in the management of other airways diseases such as asthma and COPD (chronic obstructive pulmonary disease) and have been identified as a research priority for bronchiectasis. OBJECTIVES: To assess the efficacy, cost-effectiveness and adverse effects of self-management interventions for adults and children with non-cystic fibrosis bronchiectasis. SEARCH METHODS: We searched the Cochrane Airways Specialised Register of trials, clinical trials registers, reference lists of included studies and review articles, and relevant manufacturers' websites up to 13 December 2017. SELECTION CRITERIA: We included all randomised controlled trials of any duration that included adults or children with a diagnosis of non-cystic fibrosis bronchiectasis assessing self-management interventions delivered in any form. Self-management interventions included at least two of the following elements: patient education, airway clearance techniques, adherence to medication, exercise (including pulmonary rehabilitation) and action plans. DATA COLLECTION AND ANALYSIS: Two review authors independently screened searches, extracted study characteristics and outcome data and assessed risk of bias for each included study. Primary outcomes were, health-related quality of life, exacerbation frequency and serious adverse events. Secondary outcomes were the number of participants admitted to hospital on at least one occasion, lung function, symptoms, self-efficacy and economic costs. We used a random effects model for analyses and standard Cochrane methods throughout. MAIN RESULTS: Two studies with a total of 84 participants were included: a 12-month RCT of early rehabilitation in adults of mean age 72 years conducted in two centres in England (UK) and a six-month proof-of-concept RCT of an expert patient programme (EPP) in adults of mean age 60 years in a single regional respiratory centre in Northern Ireland (UK). The EPP was delivered in group format once a week for eight weeks using standardised EPP materials plus disease-specific education including airway clearance techniques, dealing with symptoms, exacerbations, health promotion and available support. We did not find any studies that included children. Data aggregation was not possible and findings are reported narratively in the review.For the primary outcomes, both studies reported health-related quality of life, as measured by the St George's Respiratory Questionnaire (SGRQ), but there was no clear evidence of benefit. In one study, the mean SGRQ total scores were not significantly different at 6 weeks', 3 months' and 12 months' follow-up (12 months mean difference (MD) -10.27, 95% confidence interval (CI) -45.15 to 24.61). In the second study there were no significant differences in SGRQ. Total scores were not significantly different between groups (six months, MD 3.20, 95% CI -6.64 to 13.04). We judged the evidence for this outcome as low or very low. Neither of the included studies reported data on exacerbations requiring antibiotics. For serious adverse events, one study reported more deaths in the intervention group compared to the control group, (intervention: 4 of 8, control: 2 of 12), though interpretation is limited by the low event rate and the small number of participants in each group.For our secondary outcomes, there was no evidence of benefit in terms of frequency of hospital admissions or FEV1 L, based on very low-quality evidence. One study reported self-efficacy using the Chronic Disease Self-Efficacy scale, which comprises 10 components. All scales showed significant benefit from the intervention but effects were only sustained to study endpoint on the Managing Depression scale. Further details are reported in the main review. Based on overall study quality, we judged this evidence as low quality. Neither study reported data on respiratory symptoms, economic costs or adverse events. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether self-management interventions benefit people with bronchiectasis. In the absence of high-quality evidence it is advisable that practitioners adhere to current international guidelines that advocate self-management for people with bronchiectasis.Future studies should aim to clearly define and justify the specific nature of self-management, measure clinically important outcomes and include children as well as adults.

Dual antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance. OBJECTIVES: To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified studies from the Cochrane Airways Group Specialised Register (CAGR), which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine (AMED), and PsycINFO, as well as studies obtained by handsearching of journals/abstracts. We also searched the following trial registries: US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. We imposed no restriction on language of publication. We conducted our search in October 2017. SELECTION CRITERIA: We searched for randomised controlled trials comparing dual antibiotics versus a single antibiotic for short-term (< 4 weeks) or long-term management of bronchiectasis diagnosed in adults and/or children by bronchography, plain film chest radiography, or high-resolution computed tomography. Primary outcomes included exacerbations, length of hospitalisation, and serious adverse events. Secondary outcomes were response rates, emergence of resistance to antibiotics, systemic markers of infection, sputum volume and purulence, measures of lung function, adverse events/effects, deaths, exercise capacity, and health-related quality of life. We did not apply outcome measures as selection criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of 287 records, along with the full text of seven reports. Two studies met review inclusion criteria. Two review authors independently extracted outcome data and assessed risk of bias. We extracted data from only one study and conducted GRADE assessments for the following outcomes: successful treatment of exacerbation; response rates; and serious adverse events. MAIN RESULTS: Two randomised trials assessed the effectiveness of oral plus inhaled dual therapy versus oral monotherapy in a total of 118 adults with a mean age of 62.8 years. One multi-centre trial compared inhaled tobramycin plus oral ciprofloxacin versus ciprofloxacin alone, and one single-centre trial compared nebulised gentamicin plus systemic antibiotics versus a systemic antibiotic alone. Published papers did not report study funding sources.Effect estimates from one small study with 53 adults showed no evidence of treatment benefit with oral plus inhaled dual therapy for the following primary outcomes at the end of the study: successful management of exacerbation - cure at day 42 (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.22 to 2.01; 53 participants; one study; very low-quality evidence); number of participants with Pseudomonas aeruginosa eradication at day 21 (OR 2.33, 95% CI 0.66 to 8.24; 53 participants; one study; very low-quality evidence); and serious adverse events (OR 0.48, 95% CI 0.08 to 2.87; 53 participants; one study; very low-quality evidence). Similarly, researchers provided no evidence of treatment benefit for the following secondary outcomes: clinical response rates - relapse at day 42 (OR 0.57, 95% CI 0.12 to 2.69; 53 participants; one study; very low-quality evidence); microbiological response rate at day 21 - eradicated (OR 2.40, 95% CI 0.67 to 8.65; 53 participants; one study; very low-quality evidence); and adverse events - incidence of wheeze (OR 5.75, 95% CI 1.55 to 21.33). Data show no evidence of benefit in terms of sputum volume, lung function, or antibiotic resistance. Outcomes from a second small study with 65 adults, available only as an abstract, were not included in the quantitative data synthesis. The included studies did not report our other primary outcomes: duration; frequency; and time to next exacerbation; nor our secondary outcomes: systemic markers of infection; exercise capacity; and quality of life. We did not identify any trials that included children. AUTHORS' CONCLUSIONS: A small number of studies in adults have generated high-quality evidence that is insufficient to inform robust conclusions, and studies in children have provided no evidence. We identified only one dual-therapy combination of oral and inhaled antibiotics. Results from this single trial of 53 adults that we were able to include in the quantitative synthesis showed no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, serious adverse events, sputum volume, lung function, and antibiotic resistance. Further high-quality research is required to determine the efficacy and safety of other combinations of dual antibiotics for both adults and children with bronchiectasis, particularly in terms of antibiotic resistance.

Continuous versus intermittent antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events. OBJECTIVES: To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events. SEARCH METHODS: On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and full-text reports. MAIN RESULTS: We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies met our inclusion criteria. AUTHORS' CONCLUSIONS: No randomised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis. High-quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations, antibiotic resistance and the occurrence of serious adverse events.

Oral versus inhaled antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. OBJECTIVES: To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. SELECTION CRITERIA: We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection. DATA COLLECTION AND ANALYSIS: Two review authors independently applied study inclusion criteria to the searches and we planned for two authors to independently extract data, assess risk of bias and assess overall quality of the evidence using GRADE criteria. We also planned to obtain missing data from the authors where possible and to report results with 95% confidence intervals (CIs). MAIN RESULTS: We identified 313 unique records through database searches and a further 21 records from trial registers. We excluded 307 on the basis of title and abstract alone and a further 27 after examining full-text reports. No studies were identified for inclusion in the review. AUTHORS' CONCLUSIONS: There is currently no evidence indicating whether orally administered antibiotics are more beneficial compared to inhaled antibiotics. The recent ERS bronchiectasis guidelines provide a practical approach to the use of long-term antibiotics. New research is needed comparing inhaled versus oral antibiotic therapies for bronchiectasis patients with a history of frequent exacerbations, to establish which approach is the most effective in terms of exacerbation prevention, quality of life, treatment burden, and antibiotic resistance.

Macrolide antibiotics for bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life. Further evidence is required on the efficacy of macrolides in terms of specific bacterial eradication and the extent of antibiotic resistance. OBJECTIVES: To determine the impact of macrolide antibiotics in the treatment of adults and children with bronchiectasis. SEARCH METHODS: We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted all searches on 18 January 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least four weeks' duration that compared macrolide antibiotics with placebo or no intervention for the long-term management of stable bronchiectasis in adults or children with a diagnosis of bronchiectasis by bronchography, plain film chest radiograph, or high-resolution computed tomography. We excluded studies in which participants had received continuous or high-dose antibiotics immediately before enrolment or before a diagnosis of cystic fibrosis, sarcoidosis, or allergic bronchopulmonary aspergillosis. Our primary outcomes were exacerbation, hospitalisation, and serious adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of 103 records. We independently screened the full text of 40 study reports and included 15 trials from 30 reports. Two review authors independently extracted outcome data and assessed risk of bias for each study. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin.We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention.In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I2 = 65%; moderate-quality evidence). This translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 8). Data show no differences in exacerbation frequency between use of macrolides (OR 0.31, 95% CI 0.08 to 1.15; 43 participants; one study; moderate-quality evidence) and no intervention. Macrolides were also associated with a significantly better quality of life compared with placebo (MD -8.90, 95% CI -13.13 to -4.67; 68 participants; one study; moderate-quality evidence). We found no evidence of a reduction in hospitalisations (OR 0.56, 95% CI 0.19 to 1.62; 151 participants; two studies; I2 = 0%; low-quality evidence), in the number of participants with serious adverse events, including pneumonia, respiratory and non-respiratory infections, haemoptysis, and gastroenteritis (OR 0.49, 95% CI 0.20 to 1.23; 326 participants; three studies; I2 = 0%; low-quality evidence), or in the number experiencing adverse events (OR 0.83, 95% CI 0.51 to 1.35; 435 participants; five studies; I2 = 28%) in adults with macrolides compared with placebo.In children, there were no differences in exacerbation frequency (OR 0.40, 95% CI 0.11 to 1.41; 89 children; one study; low-quality evidence); hospitalisations (OR 0.28, 95% CI 0.07 to 1.11; 89 children; one study; low-quality evidence), serious adverse events, defined within the study as exacerbations of bronchiectasis or investigations related to bronchiectasis (OR 0.43, 95% CI 0.17 to 1.05; 89 children; one study; low-quality evidence), or adverse events (OR 0.78, 95% CI 0.33 to 1.83; 89 children; one study), in those receiving macrolides compared to placebo. The same study reported an increase in macrolide-resistant bacteria (OR 7.13, 95% CI 2.13 to 23.79; 89 children; one study), an increase in resistance to Streptococcus pneumoniae (OR 13.20, 95% CI 1.61 to 108.19; 89 children; one study), and an increase in resistance to Staphylococcus aureus (OR 4.16, 95% CI 1.06 to 16.32; 89 children; one study) with macrolides compared with placebo. Quality of life was not reported in the studies with children. AUTHORS' CONCLUSIONS: Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.

Personalised asthma action plans for adults with asthma.

BACKGROUND: A key aim of asthma care is to empower each person to take control of his or her own condition. A personalised asthma action plan (PAAP), also known as a written action plan, an individualised action plan, or a self-management action plan, contributes to this endeavour. A PAAP includes individualised self-management instructions devised collaboratively with the patient to help maintain asthma control and regain control in the event of an exacerbation. A PAAP includes baseline characteristics (such as lung function), maintenance medication and instructions on how to respond to increasing symptoms and when to seek medical help. OBJECTIVES: To evaluate the effectiveness of PAAPs used alone or in combination with education, for patient-reported outcomes, resource use and safety among adults with asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, clinical trial registers, reference lists of included studies and review articles, and relevant manufacturers' websites up to 14 September 2016. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), both blinded and unblinded, that evaluated written PAAPs in adults with asthma. Included studies compared PAAP alone versus no PAAP, and/or PAAP plus education versus education alone. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study characteristics and outcome data and assessed risk of bias for each included study. Primary outcomes were number of participants reporting at least one exacerbation requiring an emergency department (ED) visit or hospitalisation, asthma symptom scores on a validated scale and adverse events (all causes). Secondary outcomes were quality of life measured on a validated scale, number of participants reporting at least one exacerbation requiring systemic corticosteroids, respiratory function and days lost from work or study. We used a random-effects model for all analyses and standard Cochrane methods throughout. MAIN RESULTS: We identified 15 studies described in 27 articles that met our inclusion criteria. These 15 included studies randomised a total of 3062 participants (PAAP vs no PAAP: 2602 participants; PAAP plus education vs education alone: 460 participants). Ten studies (eight PAAP vs no PAAP; two PAAP plus education vs education alone) provided outcome data that contributed to quantitative analyses. The overall quality of evidence was rated as low or very low.Fourteen studies lasted six months or longer, and the remaining study lasted for 14 weeks. When reported, mean age ranged from 22 to 49 years and asthma severity ranged from mild to severe/high risk. PAAP alone compared with no PAAPResults showed no clear benefit or harm associated with PAAPs in terms of the number of participants requiring an ED visit or hospitalisation for an exacerbation (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.45 to 1.24; 1385 participants; five studies; low-quality evidence), change from baseline in asthma symptoms (mean difference (MD) -0.16, 95% CI -0.25 to - 0.07; 141 participants; one study; low-quality evidence) or the number of serious adverse events, including death (OR 3.26, 95% CI 0.33 to 32.21; 125 participants; one study; very low-quality evidence). Data revealed a statistically significant improvement in quality of life scores for those receiving PAAP compared with no PAAP (MD 0.18, 95% CI 0.05 to 0.30; 441 participants; three studies; low-quality evidence), but this was below the threshold for a minimum clinically important difference (MCID). Results also showed no clear benefit or harm associated with PAAPs on the number of participants reporting at least one exacerbation requiring oral corticosteroids (OR 1.45, 95% CI 0.84 to 2.48; 1136 participants; three studies; very low-quality evidence) nor on respiratory function (change from baseline forced expiratory volume in one second (FEV1): MD -0.04 L, 95% CI -0.25L to 0.17 L; 392 participants; three studies; low-quality evidence). In one study, PAAPs were associated with significantly fewer days lost from work or study (MD -6.20, 95% CI -7.32 to - 5.08; 74 participants; low-quality evidence). PAAP plus education compared with education aloneResults showed no clear benefit or harm associated with adding a PAAP to education in terms of the number of participants requiring an ED visit or hospitalisation for an exacerbation (OR 1.08, 95% CI 0.27 to 4.32; 70 participants; one study; very low-quality evidence), change from baseline in asthma symptoms (MD -0.10, 95% CI -0.54 to 0.34; 70 participants; one study; low-quality evidence), change in quality of life scores from baseline (MD 0.13, 95% CI -0.13 to 0.39; 174 participants; one study; low-quality evidence) and number of participants requiring oral corticosteroids for an exacerbation (OR 0.28, 95% CI 0.07 to 1.12; 70 participants; one study; very low-quality evidence). No studies reported serious adverse events, respiratory function or days lost from work or study. AUTHORS' CONCLUSIONS: Analysis of available studies was limited by variable reporting of primary and secondary outcomes; therefore, it is difficult to draw firm conclusions related to the effectiveness of PAAPs in the management of adult asthma. We found no evidence from randomised controlled trials of additional benefit or harm associated with use of PAAP versus no PAAP, or PAAP plus education versus education alone, but we considered the quality of the evidence to be low or very low, meaning that we cannot be confident in the magnitude or direction of reported treatment effects. In the context of this caveat, we found no observable effect on the primary outcomes of hospital attendance with an asthma exacerbation, asthma symptom scores or adverse events. We recommend further research with a particular focus on key patient-relevant outcomes, including exacerbation frequency and quality of life, in a broad spectrum of adults, including those over 60 years of age.

Interventions for bronchiectasis: an overview of Cochrane systematic reviews.

BACKGROUND: Bronchiectasis is a chronic respiratory disease characterised by abnormal dilatation of the bronchi, and presents typically with a chronic productive cough (or chronic wet cough in children) and recurrent infective exacerbations. It significantly impacts daily activities and quality of life, and can lead to recurrent hospitalisations, severe lung function impairment, respiratory failure and even death. OBJECTIVES: To provide an overview of the efficacy and safety of interventions for adults and children with bronchiectasis from Cochrane reviews.To identify gaps in the evidence base that will inform recommendations for new research and reviews, and to summarise information on reported outcomes and make recommendations for the reporting of standard outcomes in future trials and reviews. METHODS: We included Cochrane reviews of non-cystic fibrosis (CF) bronchiectasis. We searched the Cochrane Database of Systematic Reviews. The search is current to 11 February 2015. We also identified trials that were potentially eligible for, but not currently included in, published reviews to make recommendations for new Cochrane reviews. We assessed the quality of included reviews using the AMSTAR criteria. We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials and guideline data. The primary outcomes were exacerbations, lung function and quality of life. MAIN RESULTS: We included 21 reviews but extracted data from, and rated the quality of, only nine reviews that reported results for people with bronchiectasis alone. Of the reviews with no usable data, two reviews included studies with mixed clinical populations where data were not reported separately for people with bronchiectasis and 10 reviews did not contain any trials. Of the 40 studies included across the nine reviews, three (number of participants nine to 34) included children. The studies ranged from single session to year-long studies. Each review included from one to 11 trials and 28 (70%) trials in the overview included 40 or fewer participants. The total number of participants included in reviews ranged from 40 to 1040. The age range of adult participants was from 36 to 73 years and children ranged from six to 16 years. The proportion of male participants ranged from 21% to 72%. Where reported, mean baseline forced expiratory volume in one second (FEV1) ranged from 1.17 L to 1.66 L and from 47% to 88% predicted. Most of the reviews had search dates older than two years.We have summarised the published evidence as outlined in Cochrane reviews, but it was not possible to draw definitive conclusions. There was inconclusive evidence on the use of long-term antibiotics and nebulised hypertonic saline for reducing exacerbation frequency and evidence that human deoxyribonuclease (RhDNase) increases exacerbation frequency. Improvements in lung function were reported for inhaled corticosteroids (ICS) though this was small and not clinically relevant. Evidence of benefit for hyperosmolar agents and mucolytics was inconclusive. There was limited evidence of improvements in quality of life with airway clearance techniques and physical therapy but evidence of benefit for hyperosmolar agents was inconclusive. Secondary outcomes were not clearly reported in all trials in the included reviews. Improvements in dyspnoea, wheeze and cough-free days were reported for small trials of ICS and LABA (long-acting beta2-agonsts)/ICS and cough reduction was also reported for a small bromhexine trial. Reduction in sputum production was reported for long-term antibiotics and airway clearance techniques but evidence of benefit for hyperosmolar agents was inconclusive.Adverse events were included as outcomes in seven reviews. The review of long-term (four weeks to one year) prophylactic courses of antibiotics reported significantly more cases of wheeze (Peto odd ratio (OR) 8.56, 95% confidence intervals (CI) 1.63 to 44.93), dyspnoea (12 versus three, P value = 0.01) and chest pain (seven versus zero, P value = 0.01) from the same trial (74 participants) but no differences in occurrence of diarrhoea, rash or number of withdrawals. In the review of mucolytics versus placebo, relevant outcomes were not reported for erdosteine comparisons and no significant adverse effects were reported for bromhexine, though adverse events were associated with RhDNase (OR 28.19, 95% CI 3.77 to 210.85, 1 study). Of the remaining five reviews, adverse events were not reported in the single trials included in the ICS review or the physical therapy review and the impact of adverse events in the single trial included in the inhaled LABA/ICS combination versus ICS review were unclear. The reviews of short-term courses of antibiotics and inhaled hyperosmolar agents reported no significant differences in occurrence of adverse events. Fewer admissions to hospital were reported for long-term antibiotics, but this outcome was not reported in all reviews. No reviews reported differences in mortality, but again this outcome was not included in all reviews.We did not explicitly include antibiotic resistance as an outcome in the review, but this was unclear in the Cochrane reviews and evidence from other trials should be considered.We rated all reviews as high quality (AMSTAR), though opportunities for improved reporting (e.g. summary of findings and GRADE evaluation of the evidence) were identified for inclusion in future updates of the reviews. However, the majority of trials were not high quality and confidence in the effects of treatments, therefore, requires additional evidence from larger and more methodologically robust trials. We evaluated the overall coverage of important topics in bronchiectasis by mapping the quality of the current evidence base against published guidelines and identifying high priority areas for new research on; use of short-course and long-term antibiotics, ICS and oral corticosteroids, inhaled hyperosmolars, mucolytics, and use of airway clearance techniques. AUTHORS' CONCLUSIONS: This overview clearly points to significant opportunities for further research aimed at improving outcomes for people with bronchiectasis. We have highlighted important endpoints for studies (particularly exacerbations, quality of life and lung function), and areas of clinical practice that are in most urgent need of evidence-based support (including long-term antibiotics, ICSs and mucolytics).As the evidence is confined to small trials of short duration, it is not currently possible to assess the balance between the benefits and potential harms of treatments for bronchiectasis.

Exploring the outcomes in studies of primary frozen shoulder: is there a need for a core outcome set?

PURPOSE: In our study we explored the need to define a core outcome set for primary frozen shoulder. METHODS: We investigated the outcomes used by studies included in a systematic review of the management of primary frozen shoulder; surveyed which primary outcome measures health care professionals considered important; and re-examined papers previously obtained for a systematic review of patients' views of interventions for frozen shoulder to investigate their views on outcomes. RESULTS: Thirty-one studies investigated the outcomes range of movement (28 studies), pain (22), function and disability (22), adverse events (13), quality of life (7) and other outcomes (5). Many different types of pain and ranges of movement were measured. Function and disability was measured using fifteen instruments, the content of which varied considerably. Function and disability, pain and range of movement (132, 108 and 104 respondents, respectively) were most often cited by health care professionals as the primary outcome measure that should be used. Searches identified one paper that included patients' views. Outcomes of importance to patients were pain at night, general pain, reduced mobility (resulting in modification of activities) and the emotional impact of frozen shoulder. CONCLUSIONS: We identified a diverse range of outcomes that have been used or are considered to be important. The development of a core outcome set would improve the design and reporting of studies and availability of data for evidence synthesis. Methods used to develop a core outcome set should be robust, transparent and reflect the views of all stakeholders.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane review published in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. SEARCH METHODS: We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis. We used the GRADE system to summarise the quality of evidence for core comparisons. MAIN RESULTS: We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low-quality evidence) and that rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low-quality evidence). We found a short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies (low-quality evidence, standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to -0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain, which does not exceed the pre-established criteria for a minimal clinically important difference (≥ 15%). Evidence for multiple-dose studies was heterogenous but did not demonstrate a significant effect (very low-quality evidence).For CES (six studies, 270 participants) no statistically significant difference was found between active stimulation and sham (low-quality evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation (very low-quality evidence). Pre-specified subgroup analysis of tDCS applied to the motor cortex (n = 183) did not demonstrate a statistically significant effect and this lack of effect was consistent for subgroups of single or multiple-dose studies.One small study (n = 91) at unclear risk of bias suggested a positive effect of RINCE over sham stimulation on pain (very low-quality evidence).Non-invasive brain stimulation appears to be frequently associated with minor and transient side effects, though there were two reported incidences of seizure related to active rTMS in the included studies. AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. It is likely that multiple sources of bias may exaggerate this observed effect. The effects do not meet the predetermined threshold of minimal clinical significance and multiple-dose studies do not consistently demonstrate effectiveness. The available evidence suggests that low-frequency rTMS, rTMS applied to the pre-frontal cortex, CES and tDCS are not effective in the treatment of chronic pain. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation and the conclusion regarding the effectiveness of tDCS has changed. We recommend that previous readers should re-read this update. There is a need for larger, rigorously designed studies, particularly of longer courses of stimulation. It is likely that future evidence may substantially impact upon the presented results.

Leukodepletion for patients undergoing heart valve surgery.

BACKGROUND: There is some evidence for the benefits of leukodepletion in patients undergoing coronary artery surgery. Its effectiveness in higher risk patients, such as those undergoing heart valve surgery, particularly in terms of overall clinical outcomes, is currently unclear. OBJECTIVES: To assess the beneficial and harmful effects of leukodepletion on clinical, patient-reported and economic outcomes in patients undergoing heart valve surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 3 of 12) in The Cochrane Library, the NHS Economic Evaluations Database (1960 to April 2013), MEDLINE Ovid (1946 to April week 2 2013), EMBASE Ovid (1947 to Week 15 2013), CINAHL (1982 to April 2013) and Web of Science (1970 to 17 April 2013) on 19 April 2013. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), the US National Institutes of Health (NIH) clinical trials database and the International Standard Randomised Controlled Trial Number Register (ISRCTN) in April 2013 for ongoing studies. No language or time period restrictions were applied. We examined the reference lists of all included randomised controlled trials and contacted authors of identified trials. We searched the 'grey' literature at OpenGrey and handsearched relevant conference proceedings. SELECTION CRITERIA: Randomised controlled trials comparing a leukocyte-depleting arterial line filter with a standard arterial line filter, on the arterial outflow of the heart-lung bypass circuit, in elective patients undergoing heart valve surgery. DATA COLLECTION AND ANALYSIS: Data were collected on the study characteristics, three primary outcomes (1. post-operative in-hospital all-cause mortality within three months, 2. post-operative all-cause mortality excluding inpatient mortality < 30 days, 3. length of stay in hospital, 4. adverse events and serious adverse events) and seven secondary outcomes (1. tubular or glomerular kidney injury, 2. validated health-related quality of life scales, 3. validated renal injury scales, 4. use of continuous veno-venous haemo-filtration, 5. length of stay in intensive care, 6. costs of care). Data were extracted by one author and verified by a second author. Insufficient data were available to perform a meta-analysis or sensitivity analysis. MAIN RESULTS: Eight studies were eligible for inclusion in the review but data on prespecified review outcomes were available from only one, modestly powered (24 participants) study (Hurst 1997). There were no differences between a leuko-depleting versus standard filter in length of stay in the intensive care unit (ICU) (mean difference (MD) 0.80 days; 95% confidence interval (CI) -0.24 to 1.84) or length of hospital stay (MD 0.20 days; 95% CI -1.78 to 2.18). AUTHORS' CONCLUSIONS: There are currently insufficient good quality trials with valve surgery patients to inform recommendations for changes in clinical practice. A future National Institute for Health Research (NIHR)-funded feasibility study (recruiting mid-year 2013) comparing leukodepletion with a standard arterial line filter in patients undergoing elective heart valve surgery (the ROLO trial) will be the largest study to date and will make a significant contribution to future updates of this review.

Advanced clinical practice in paediatric haematology and oncology: developing a capability document.

Specialist roles have been developed to provide holistic care to children and young people with cancer, one of which is the advanced clinical practitioner (ACP) in paediatric oncology and haematology. A survey showed that paediatric oncology and haematology ACPs in the UK work in a wide variety of roles and that their numbers vary greatly between treatment centres. The survey also confirmed the need for a national standardised framework delineating the knowledge, skills and expertise required of ACPs working in paediatric oncology and haematology. This article describes the development of a capability document to support and standardise advanced practice in paediatric oncology and haematology. The document reflects the advanced level of critical thinking, autonomy and decision-making required of ACPs and has been endorsed by the Children's Cancer and Leukaemia Group and by the Royal College of Nursing. It is hoped that it will support ACPs to consistently deliver high-quality, safe care for the benefit of children and young people with cancer and their families.