Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review

Introduction:Cystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF.Methods: We searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps.Results: There were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation—most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1).Conclusions: We have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials.PROSPERO registration number: Pre-results; CRD42015030111

Working with the patient and clinical community to deliver clinical research in cystic fibrosis: James Lind CF Phase II

This is a protocol which sets out the aims, objectives and commitments of the second phase of the James Lind Alliance Priority Setting Partnership in Cystic Fibrosis and the basic roles and responsibilities of the partners therein. The James Lind Alliance Priority Setting Partnership in cystic fibrosis was carried out in 2016 using a robust and widely accepted methodology to develop the top 10 questions for clinical research in CF, through discussions with both the clinical and patient community.We now aim to explore four of the top ten questions from this process and develop them into a series of testable hypotheses for clinical research. Where the hypothesis will be tested in a clinical trial, we will develop a PICO question for each hypothesis (Population, Intervention, Comparator & Outcome). We will use online surveys and focus groups to achieve our aim

Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis

Background Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review. Objectives To compare biofilm antimicrobial susceptibility testing‐driven therapy to conventional antimicrobial susceptibility testing‐driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 07 April 2020. We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 07 April 2020 and 05 September 2017. Selection criteria Randomized controlled trials (RCTs) of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis. Data collection and analysis Two authors independently selected RCTs, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria. Main results The searches identified two multicentre, double‐blind RCTs eligible for inclusion in the review with a total of 78 participants (adults and children); one RCT was undertaken in people who were clinically stable, the second was in people experiencing pulmonary exacerbations. Both RCTs prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy. Although the intervention was shown to be safe, the data from these two RCTs did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both RCTs had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected. Authors' conclusions The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [5 February 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [updated 13 July 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein

Cycling infrastructure for reducing cycling injuries in cyclists

Background: Cycling is an attractive form of transport. It is beneficial to the individual as a form of physical activity that may fit more readily into an individual’s daily routine, such as for cycling to work and to the shops, than other physical activities such as visiting a gym. Cycling is also beneficial to the wider community and the environment as a result of fewer motorised journeys. Cyclists are seen as vulnerable road users who are frequently in close proximity to larger and faster motorised vehicles. Cycling infrastructure aims to make cycling both more convenient and safer for cyclists. This review is needed to guide transport planning. Objectives: To: 1. evaluate the effects of different types of cycling infrastructure on reducing cycling injuries in cyclists, by type of infrastructure; 2. evaluate the effects of cycling infrastructure on reducing the severity of cycling injuries in cyclists; 3. evaluate the effects of cycling infrastructure on reducing cycling injuries in cyclists with respect to age, sex and social group. Search methods: We ran the most recent search on 2nd March 2015. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), Embase Classic + Embase(OvidSP), PubMed and 10 other databases. We searched websites, handsearched conference proceedings, screened reference lists of included studies and previously published reviews and contacted relevant organisations. Selection criteria: We included randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted time series studies which evaluated the effect of cycling infrastructure (such as cycle lanes, tracks or paths, speed management, roundabout design) on cyclist injury or collision rates. Studies had to include a comparator, that is, either no infrastructure or a different type of infrastructure. We excluded studies that assessed collisions that occurred as a result of competitive cycling. Data collection and analysis: Two review authors examined the titles and abstracts of papers obtained from searches to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. We carried out a meta-analysis using the random-effects model where at least three studies reported the same intervention and outcome. Where there were sufficient studies, as a secondary analysis we accounted for changes in cyclist exposure in the calculation of the rate ratios. We rated the quality of the evidence as ‘high’, ‘moderate’,‘low’ or ‘very low’ according to the GRADE approach for the installation of cycle routes and networks. Main results: We identified 21 studies for inclusion in the review: 20 controlled before-after (CBA) studies and one interrupted time series (ITS) study. These evaluated a range of infrastructure including cycle lanes, advanced stop lines, use of colour, cycle tracks, cycle paths, management of the road network, speed management, cycle routes and networks, roundabout design and packages of measures. No studies reported medically-attended or self-reported injuries. There was no evidence that cycle lanes reduce the rate of cycle collisions (rate ratio 1.21, 95% CI 0.70 to 2.08). Taking into account cycle flow, there was no difference in collisions for cyclists using cycle routes and networks compared with cyclists not using cycle routes and networks (RR 0.40, 95% CI 0.15 to 1.05). There was statistically significant heterogeneity between the studies (I² = 75%, Chi² = 8.00 df = 2, P = 0.02) for the analysis adjusted for cycle flow. We judged the quality of the evidence regarding cycle routes and networks as very low and we are very uncertain about the estimate. These analyses are based on findings from CBA studies. From data presented narratively, the use of 20 mph speed restrictions in urban areas may be effective at reducing cyclist collisions. Redesigning specific parts of cycle routes that may be particularly busy or complex in terms of traffic movement may be beneficial to cyclists in terms of reducing the risk of collision. Generally, the conversion of intersections to roundabouts may increase the number of cycle collisions. In particular, the conversion of intersections to roundabouts with cycle lanes marked as part of the circulating carriageway increased cycle collisions. However, the conversion of intersections with and without signals to roundabouts with cycle paths may reduce the odds of collision. Both continuing a cycle lane across the mouth of a side road with a give way line onto the main road, and cycle tracks, may increase the risk of injury collisions in cyclists. However, these conclusions are uncertain, being based on a narrative review of findings from included studies. There is a lack of evidence that cycle paths or advanced stop lines either reduce or increase injury collisions in cyclists. There is also insufficient evidence to draw any robust conclusions concerning the effect of cycling infrastructure on cycling collisions in terms of severity of injury, sex, age, and level of social deprivation of the casualty. In terms of quality of the evidence, there was little matching of intervention and control sites. In many studies, the comparability of the control area to the intervention site was unclear and few studies provided information on other cycling infrastructures that may be in place in the control and intervention areas. The majority of studies analysed data routinely collected by organisations external to the study team, thus reducing the risk of bias in terms of systematic differences in assessing outcomes between the control and intervention groups. Some authors did not take regression-to-mean effects into account when examining changes in collisions. Longer data collection periods pre- and post-installation would allow for regression-to-mean effects and also seasonal and time trends in traffic volume to be observed. Few studies adjusted cycle collision rates for exposure. Authors’ conclusions: Generally, there is a lack of high quality evidence to be able to draw firm conclusions as to the effect of cycling infrastructure on cycling collisions. There is a lack of rigorous evaluation of cycling infrastructure

Do guidelines for treating chest disease in children use Cochrane Reviews effectively?: a systematic review

Cochrane Reviews summarise best evidence and should inform guidelines. We assessed the use of Cochrane Reviews in the UK guidelines for paediatric respiratory disease. We found 21 guidelines which made 1025 recommendations, of which 96 could be informed by a Cochrane Review. In 38/96 recommendations (40%), some or all of the relevant Cochrane Reviews were not cited. We linked recommendations to 140 Cochrane Reviews. In 37/140 (26%) cases, the guideline recommendation did not fully agree with the Cochrane Review. Guideline developers may fail to use Cochrane Reviews or may make recommendations which are not in line with best evidence

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [updated 13 July 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein

Is microfinance associated with changes in women's wellbeing and children's nutrition? a systematic review and meta-analysis

Background: Microfinance is the provision of savings and small loans services, with no physical collateral. Most recipients are disadvantaged women. The social and health impacts of microfinance have not been comprehensively evaluated.Objective: To explore the impact of microfinance on contraceptive use, female empowerment and children’s nutrition in South Asia, Sub-Saharan Africa and Latin America and the Caribbean.Design: We conducted a systematic search of published and grey literature (1990–2018), with no language restrictions. We conducted meta-analysis, where possible, to calculate pooled ORs. Where studies could not be combined, we described these qualitatively.Data sources: EMBASE, MEDLINE, LILACS, CENTRAL and ECONLIT were searched (1990–June 2018).Eligibility criteria: We included controlled trials, observational studies and panel data analyses investigating microfinance involving women and children.Data extraction and synthesis :Two independent reviewers extracted data and assessed risk of bias. The methodological quality of included studies was assessed using the Cochrane risk-of-bias tool for controlled trials and quasi-experimental studies and a modified Newcastle Ottawa Scale for cross-sectional surveys and analyses of panel data. Meta-analyses were conducted using STATA V.15 (StataCorp).Results: We included 27 studies. Microfinance was associated with a 64% increase in the number of women using contraceptives (OR 1.64, 95% CI 1.45 to 1.86). We found mixed results for the association between microfinance and intimate partner violence. Some positive changes were noted in female empowerment. Improvements in children’s nutrition were noted in three studies.Conclusion: Microfinance has the potential to generate changes in contraceptive use, female empowerment and children’s nutrition. It was not possible to compare microfinance models due to the small numbers of studies. More rigorous evidence is needed to evaluate the association between microfinance and social and health outcomes