Cochrane Cystic Fibrosis & Genetic Disorders Group...Cochrane Cystic Fibrosis and Genetic Disorders Review Group Page 2 Methodological Expectations of Cochrane Intervention Reviews

Cochrane Cystic Fibrosis and Genetic Disorders Review Group Page 1

November 2012 Issue 45

- Current Titles Registered -

• Enzyme replacement and substrate reduction

therapy for Gaucher disease

• Exercise for haemophilia

• Gene therapy for hemophilia

• Immune tolerance induction for treating inhibitors

in people with haemophilia A or B

• Interventions for caregivers for the recognition of

disease-related complications in children with

sickle cell anaemia

• Interventions for improving adherence to

treatment for CF

• Interventions for silent cerebral infarcts in people

with sickle cell disease

• Interventions for treating intrahepatic cholestasis

in people with sickle cell disease

• Interventions for treating acute bleeding

episodes in people with acquired hemophilia

• Non-surgical interventions for treating

menorrhagia in women with bleeding disorders

• Preconception risk assessment for

thalassaemia, sickle cell disease, CF and Tay-

Sachs disease

• Psychological therapies for people with

hemophilia and their families

• Rituximab for treating inhibitors in children with

hemophilia

• Splenectomy for people with thalassaemia major

and intermedia

• Stop codon mutation-specific therapies for CF

• Sweat test for the diagnosis of CF

• Treatment for osteoporosis in people with beta

thalassaemia

• Vitamin D supplementation for sickle cell disease

Cochrane Cystic Fibrosis & Genetic Disorders Group

Output of the CFGD Group

115 reviews & 24 protocols published on Issue 12 2012 of The Cochrane Library

Editorial: Update of output &

promotional activities

Tracey Remmington, Managing Editor

What’s Inside: Editorial 1

Current titles registered 1

New Cochrane CEO 2

Methodological Expectations (MECIR) 2

20th Cochrane Colloquium, NZ 3

Cochrane 21st Anniversary Symposium 4

An interesting article …. 4

New reviews 5-11

2013 timetables - Cochrane workshops 12

Contact details for Cochrane Centres 13

Contact form 14

Summary sheet of the CFGD Group 15

Latest Group output 16-18

It has been another good year for the production

of reviews by the CFGD Group. We have

produced a further 10 reviews this year,

bringing our total to 115 published reviews. The

majority of these are in CF and sickle cell

disease, but we are actively working on

producing more reviews in coagulopathies and

inborn errors of metabolism. While it remains

important to increase our output, there is a

corresponding need to ensure that these

reviews are accessed and utilised by

consumers, clinicians and policy makers. We

are therefore also working to promote these

reviews in numerous ways. Two strategies

recently employed are referred to below.

Pediatric Respiratory Reviews

We have recently started submitting articles for

a ‘Cochrane Corner’ to the journal – Paediatric

Respiratory Reviews (Elsevier). These short

summaries are a great way of promoting the

cystic fibrosis reviews produced by the CFGD

Group and enable us to reach a wider audience.

The articles are published quarterly and are

proving to be popular with the journal’s

readership.

Cochrane Podcasts

We have also starting to ask some review

authors to record podcasts of their new reviews.

These are freely available on the following

website: http://www.cochrane.org/podcasts/

http://www.cochrane.org/podcasts/


Methodological Expectations of Cochrane Intervention Reviews (MECIR)

Nikki Jahnke Managing Editor

The Methodological Expectations of Cochrane Intervention Reviews (MECIR) project aims to specify

methodological expectations for Cochrane Protocols, Reviews, and updates of reviews on the effects of

interventions, and to ensure that these methodological expectations are supported and implemented

across The Cochrane Collaboration. The MECIR project team have now finalized standards for the

reporting of Cochrane Intervention Reviews which have been developed in consultation with people from

inside and outside The Cochrane Collaboration and are now available from the CEU website

www.editorial-unit.cochrane.org/mecir.

The reporting standards complement work that has already identified standards for the conduct of our

reviews. They are not intended to apply to protocols or updated reviews at this point – these will be

addressed in further work in the future. As with the standards for conduct we have designated each

reporting item to be either mandatory (compliance required for publication) or highly desirable (expected

but may be justifiably not done). The project team have also provided a rationale for each standard and

indicated any relevant conduct standards or locations in the Cochrane Handbook. The reporting

standards will be subject to review in 2013.

There is also a separate project ongoing aimed at clarifying expectations for plain language summaries

(PLEACS: http://consumers.cochrane.org/PLEACS). Plain language summaries fulfil an important

function in Cochrane Reviews. Aimed at a broad readership they convey the review question and the

findings in terms that are accessible to consumers and non-expert readers. The draft standards

presented on the CEU website have been developed by a committee led by the Consumer Coordinator,

Catherine McIlwain. The finalization of these standards based on comments received from external and

internal consultation is currently in process.

The Cochrane Collaboration has adopted recommendations provided in the PRISMA statement

(www.prisma-statement.org). We believe the new reporting standards will ensure compliance with these

recommendations. Extensions to the PRISMA statement may also be relevant to particular reviews, such

as reviews addressing equity issues [http://equity.cochrane.org/equity-extension-prisma].

New CEO for The Cochrane Collaboration Mark Wilson has been appointed new Chief Executive Officer of The Cochrane

Collaboration and will be based at the Cochrane Operations Unit in the UK. He has joined

The Collaboration from his post of Executive Director of Panos London, part of a global

network of institutes that aims to ensure information is effectively used to foster public

debate, pluralism and democracy, focusing particularly on development of the media and

information and communication technologies in lower income countries. He has previous extensive

leadership experience at the highest levels in international humanitarian and development

organisations, including the International Federation of the Red Cross and Red Crescent Societies. He

is a member of the Royal Institute of International Affairs and the International Institute for Strategic

Studies. As a former journalist in London and Hong Kong, and Communications Director of the Swiss-

based Business Council for Sustainable Development, he is an experienced commentator on

economics, business and politics. As his background indicates, he shares the ethos and values of the

Collaboration, and we look forward to his leadership of our organization.

http://www.editorial-unit.cochrane.org/mecir









http://consumers.cochrane.org/PLEACS







http://www.prisma-statement.org/







http://equity.cochrane.org/equity-extension-prisma












20th Cochrane Colloquium Auckland 30th Sept – 3rd Oct 2012

Nikki Jahnke Managing Editor

As we previously reported the 2012 Cochrane Colloquium was to have been held in China. However,

changes in Chinese government policy governing scientific meetings made it impossible and the New

Zealand Branch of the Australasian Cochrane Centre stepped in to host the 2012 Colloquium in Auckland,

New Zealand, 30 September to 3 October. The theme of the 20th Cochrane Colloquium was 'Evidence

around the globe'.

The organisers were able to make numerous sessions available to those unable to attend by posting

videos online. Downloads including of the varied plenary sessions can still be accessed at:

http://webcast.gigtv.com.au/Mediasite/Catalog/catalogs/colloquium/?state=TCx5QTU8gNoAe9ApWdro.

Topics ranged from the reliability of evidence used in making healthcare decisions and producing reviews

presenting the best evidence with the greatest impact to how systematic reviews can influence future

research and review methodology and how we at Cochrane can get this message out globally. Posters are

now also available to view online at http://colloquium.cochrane.org/posters. A number of prizes are

awarded at each Cochrane Colloquium and this years winners are listed below.

The Kenneth Warren Prize is awarded to the principal author of a systematic review published in the

CDSR and authored by a national living in a developing country, that is judged to be both of

high methodological quality and relevant to health problems in developing countries. The winner for 2012

was Don Mathanga (Cochrane Infectious Diseases Group and University of Malawi, Malaria Alert Center)

for his review ‘Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women’

which is published on The Cochrane Library.

The Chris Silagy Prize is for contributions to The Cochrane Collaboration that are often insufficiently

recognised; e.g., administration, management, Colloquium organisation, communication and motivation - in

short, the 'glue' that helps to keep The Cochrane Collaboration together. In 2012 this was awarded to Jordi

Pardo who is currently the Managing Editor of the Musculoskeletal Group and an author with four other

groups; he also has organised previous colloquia and sits on a number of Collaboration-wide committees.

The Thomas C Chalmers Award is given to the principal author of both the best oral and the best poster

presentation addressing methodological issues related to systematic reviews given by an early career

investigator. This was won in 2012 by Alison O'Mara-Eves for her poster on alternative systematic ways of

identifying relevant evidence for broad review questions: O'Mara-Eves AJ, Brunton G, Thomas J,

Kavanagh J, Oliver S. Systematic methods for identifying evidence for broad review questions: looking

beyond titles and abstracts. Proceedings of the Twentieth Cochrane Colloquium, 2012. The oral

presentation award was won by Matthew Page: Page MJ, McKenzie JE, Green SE, Forbes A. Types of

selective inclusion and reporting bias in randomised trials and systematic reviews of randomised trials.

Proceedings of the Twentieth Cochrane Colloquium, 2012.

Finally, the Bill Silverman Prize acknowledges explicitly the value of criticism of The Cochrane

Collaboration, with a view to helping to improve its work. In 2012 this prize was awarded to Mona Nasser

for her paper on ensuring the relevance of Cochrane reviews. Nasser M, Welch V, Tugwell P, Ueffing E,

Doyle J, Waters E. Ensuring relevance for Cochrane reviews: evaluating processes and methods for

prioritizing topics for Cochrane reviews. J Clin Epidemiol 2012 Apr 19.

Lesley Gillespie, former TSC with the Bone, Muscle and Trauma Group, was presented with a one-off

award as lead author on the Cochrane review that received the highest number of full text accesses for the

last 7 years and for the most cited review for the last 10 years: Interventions for preventing falls in elderly

people (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000340.pub2/abstract).

http://webcast.gigtv.com.au/Mediasite/Catalog/catalogs/colloquium/?state=TCx5QTU8gNoAe9ApWdro















http://colloquium.cochrane.org/posters







http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000340.pub2/abstract




















An interesting article ……

Veerus P, Fischer K, Hakama M, Hemminki E.

Results from a blind and a non-blind randomised trial run in parallel: experience

from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial.

BMC Medical Research Methodology 2012, 12:44 (4 April 2012)

Cochrane UK & Ireland 21st Anniversary Symposium - Oxford, UK Nikki Jahnke Managing Editor

The 18th Annual Meeting of UK- and Ireland-based contributors to The Cochrane Collaboration will be

combined with the Cochrane Collaboration Steering Group’s mid-year meeting at the Collaboration’s 21st

Anniversary Symposium in 2013. The Symposium is being held at The Saїd Business School in Oxford

on 20th & 21st March 2013 and registration is now open.

The theme for the Symposium is ‘Cochrane’s challenge’ and will involve glancing back to the

achievements of the last 21 years as well as looking ahead to the next set of challenges the Cochrane

Collaboration faces. The Collaboration will be celebrating its 21st Anniversary in the UK with a drinks

reception (including birthday cake) to be held at The Saїd Business School on the Wednesday evening

(17:30 – 18:30) for all registered Symposium and Mid-year Meeting delegates.

During the Symposium, there will be four plenary sessions; in the opening session Chief Medical Officer

and our own CFGD Haemoglobinopathies Editor, Professor Dame Sally Davies along with Andrew Dilnot

(economist, broadcaster and Chair of the UK Statistics Authority) will review the background to the

challenges we face and provide some insights into why we have to think differently in the 20 years ahead.

The second plenary session will consider the challenge of over-diagnosis and over-treatment. Speakers

Dr Steven Woloshin and Dr Lisa Schwartz will discuss how Cochrane can help in preventing people

being made “sick in the pursuit of health”. The challenge of communication is the focus of the third

session when André Tomlin from evidence-based healthcare consultancy Minervation Ltd., will explain

how social media and cutting edge communication tools can be used to disseminate high quality

evidence. He will be joined by Tracey Brown from Sense about Science, a charitable trust that equips

people to make sense of scientific and medical claims in public discussion. The closing plenary session

will see Dr Ben Goldacre, prize-winning science journalist and author, offer his view of the challenges

facing the Collaboration in the next 20 years. In response, David Tovey (Editor-in-chief) and Mark Wilson

(Chief Executive Officer) of The Cochrane Collaboration, will present their vision of the years ahead and

how the challenges outlined during the meeting might best be met.

There is a change to the usual format for contributors’ meetings. At this meeting there will not be any

sessions for presenting posters. Furthermore, in a change to the usual format for workshops, on

Thursday afternoon there will be a short introduction session focusing on the best ways to engage with

patients, healthcare organizations, professional groups, commissioners and others. After this session

delegates will be able to choose from a number of workshops and master-classes which will consider this

topic. Engagement is vital to ensure that Cochrane does the right reviews, at the right time, examining the

right outcomes and evaluating the right treatments if it is to meet the challenge of its outputs being both

relevant and timely. For more information, please go to oxford2013.cochrane.org.

http://www.biomedcentral.com/1471-2288/12/44

http://www.sbs.ox.ac.uk/Pages/default.aspx







http://www.oxford2013.cochrane.org/






Reviewers: Amin R, Waters V

Abstract

Background

Stenotrophomonas maltophilia is one of the most common emerging multi-drug resistant organisms found

in the lungs of people with cystic fibrosis and its prevalence is increasing. Chronic infection

with Stenotrophomonas maltophilia has recently been shown to be an independent predictor of pulmonary

exacerbation requiring hospitalization and antibiotics. However, the role of antibiotic treatment

of Stenotrophomonas maltophilia infection in people with cystic fibrosis is still unclear.

Objectives

The objective of our review is to assess the effectiveness of antibiotic treatment for Stenotrophomonas

maltophilia in people with cystic fibrosis. The primary objective is to assess this in relation to lung function

and pulmonary exacerbations in the setting of acute pulmonary exacerbations. The secondary objective is

to assess this in relation to the eradication of Stenotrophomonas maltophilia.

Search strategy

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches

and handsearching of journals and conference abstract books. We also searched a registry of ongoing

trials and the reference lists of relevant articles and reviews.

Date of latest search: 06 July 2011.

Selection criteria

Any randomized controlled trial of Stenotrophomonas maltophilia mono-infection or Stenotrophomonas

maltophilia co-infection withPseudomonas aeruginosa in either the setting of an acute pulmonary

exacerbation or a chronic infection treated with suppressive antibiotic therapy.

Data collection & analysis

Both authors independently assessed the trials identified by the search for potential inclusion in the review.

Main results

The initial search strategy identified only one study of antibiotic treatment of pulmonary exacerbations that

included cystic fibrosis patients with Stenotrophomonas maltophilia. However, this study had to be

excluded because data was not available per pathogen.

Authors' conclusions

This review did not identify any evidence regarding the effectiveness of antibiotic treatment

for Stenotrophomonas maltophilia in people with cystic fibrosis. Until such evidence becomes available,

clinicians need to use their clinical judgement as to whether or not to treat Stenotrophomonas

maltophilia infection in patients with cystic fibrosis. Randomized clinical trials are needed to address these

unanswered clinical questions.


New review – Issue 5, 2012

Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis

Reviewers: Burgess L, Southern KW

Abstract

Background

Invasive pneumococcal disease is associated with significant mortality and many countries have introduced

routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal

disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against

pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is

currently recommended for all children and adults with cystic fibrosis.

Objectives

To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis.

Search strategy

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register,

which comprises references identified from comprehensive electronic database searches and

handsearches of relevant journals and abstract books of conference proceedings. In addition, the

pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were

approached.

Date of the most recent search: 10 July 2012.

Selection criteria

Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a

polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults

with cystic fibrosis were eligible for inclusion.


No relevant trials were identified.

Main results

There are no trials included in this review.


As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal

immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now

include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future

randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the

opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in

people with cystic fibrosis.



Pneumococcal vaccines for cystic fibrosis

Reviewers: Horsley A, Jones AM

Abstract Background Chronic pulmonary infection is one of the hallmarks of lung disease in cystic fibrosis. Infections dominated

by organisms of the Burkholderia cepacia complex, a group of at least 17 closely-related species of gram-

negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant

necrotising pneumonia, and are greatly feared by patients. Burkholderia cepaciabacteria are innately

resistant to many common antibiotics and able to acquire resistance against many more. Since strict patient

segregation was introduced to cystic fibrosis medical care, the incidence of the more virulent epidemic

strains has fallen, and new infections are more likely to be with environmentally-acquired strains which

seem to exhibit less virulence. Nonetheless, exacerbations of respiratory symptoms require effective

therapy directed against the dominant bacterial species. Although evidence-based guidelines exist for the

treatment of respiratory exacerbations involving Pseudomonas aeruginosa, the most common chronic

infection in cystic fibrosis, these cannot be directly extended to Burkholderia cepacia complex infections.

The aim of this review is to assess the available trial evidence for choice and application of treatments

for Burkholderia cepacia complex infections.

Objectives To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis

experiencing an exacerbation, who are chronically infected with organisms of the Burkholderia

cepacia complex.

Search strategy We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches

and handsearching of journals and conference abstract books. We also searched the reference lists of

relevant articles and reviews.

Date of latest search: 29 November 2011.

Selection criteria Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary

symptoms in cystic fibrosis patients chronically infected with organisms of the Burkholderia

cepacia complex.

Data collection & analysis No relevant trials were identified.

Main results No trials were included in this review.

Authors' conclusions Burkholderia cepacia complex infections present a significant challenge for cystic fibrosis clinicians and

patients alike. The incidence is likely to increase as the cystic fibrosis population ages and the problem of

how to manage and treat these infections becomes more important. There is a lack of trial evidence to

guide decision making and no conclusions can be drawn from this review about the optimal antibiotic

regimens for cystic fibrosis patients with chronic Burkholderia cepacia complex infections. Clinicians must

continue to assess each patient individually, taking into account in vitro antibiotic susceptibility data,

previous clinical responses and their own experience. There is a clear need for multi-centre randomised

clinical trials to assess the effectiveness of different antibiotic regimens in cystic fibrosis patients infected

with organisms of the Burkholderia cepacia complex.



Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary exacerbation

Reviewers: Waters V, Ratjen F

Abstract Background The antibiotics used to treat pulmonary infections in people with cystic fibrosis are typically chosen 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 cystic fibrosis patients 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.

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.


and handsearching of journals and conference abstract books. We also searched a registry of ongoing

trials and the reference lists of relevant articles and reviews.

Most recent search: 02 August 2012.

Selection criteria Randomized controlled trials 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 individuals with cystic fibrosis.

Data collection & analysis Both authors independently selected trials, assessed their risk of bias and extracted data from eligible trials.

Additionally, the authors contacted the trial investigators to obtain further information.

Main results The search identified one multicentre, randomized, double-blind controlled clinical trial eligible for inclusion

in the review (39 participants). This trial 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. The mean

(standard deviation) change in density in log10 colony forming units per gram was -2.94 (2.83) in the biofilm

group and -3.27 (3.09) in the control group, for a mean difference of 0.28 (95% confidence interval -1.98 to

2.54) (P = 0.8). The data did not provide evidence that biofilm susceptibility testing was superior to

conventional susceptibility testing.

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. Future randomized clinical

trials on this topic may shed further light on this question.



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

Reviewers: Martí-Carvajal AJ, Knight-Madden JM, Martinez-Zapata MJ

Abstract Background The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with

sickle cell disease. Many treatment options are available to the healthcare professional, although it is

uncertain which treatments have been assessed for effectiveness in people with sickle cell disease.

Objectives To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle

cell disease.

Search strategy We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials

Register. We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI

Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health

Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted

those groups or individuals who may have completed relevant randomised trials in this area.

Date of the last search of the Group's Haemoglobinopathies Trials Register: 25 May 2012.

Selection criteria Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease

compared to placebo or an alternative treatment.

Data collection & analysis Two authors independently selected studies for inclusion. All three authors independently assessed the risk

of bias of the included studies and extracted data.

Main results Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different

intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-

cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, RGD

peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine

butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size

compared with a control group, mean reduction 6.60cm2 (95% CI 5.51 to 7.69). Three trials reported on the

incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix). None reported a

significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following

treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no

reported information on the safety of these interventions.

Authors' conclusions There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants

compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with

these reports. We planned to analyse results according to general groups: pharmaceutical interventions

(systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we

were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between

the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified

trials, prevented us performing any meta-analyses. This Cochrane review provides some evidence for the

effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as

having a high risk of bias due to inadequacies in the single trial report. Other included studies were also

assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution.

The safety profile of the all interventions was inconclusive.



Interventions for treating leg ulcers in people with SCD

Reviewers: Waters V, Ratjen F

Abstract Background Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium

tuberculosis complex, which are commonly found in the environment. Nontuberculous mycobacteria

species (most commonly Mycobacterium avium complex andMycobacterium abscessus) are isolated from

the respiratory tract of approximately 5% to 20% of individuals with cystic fibrosis; they can cause lung

disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in

certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous

mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is

not clear which antibiotic regimen may be the most effective in the treatment of these patients.

Objectives The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare

different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people

with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and

pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess

treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters,

hospitalizations and use of oral antibiotics.


and hand searching of journals and conference abstract books. Date of last search: 19 July 2012.

We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date

of last search: 10 August 2012.

Selection criteria Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic

treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another

nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis.

Data collection & analysis Data were not collected because no completed trials were identified by the searches.

Main results No completed trials were identified by the searches, but one ongoing trial was identified, which seems

eligible for inclusion in this review when completed.

Authors' conclusions This review did not find any evidence for the effectiveness of different antimicrobial treatment for

nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes

available, it is reasonable for clinicians to follow the American Thoracic Society guidelines for the diagnosis

and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex

or Mycobacterium abscessus in patients with cystic fibrosis.



Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis

Reviewers: Gerard Ryan, Nikki Jahnke, Tracey Remmington

Abstract Background Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to

persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe.

Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or

in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe

infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may

prove an alternative in people with poor access to their veins.

Objectives

To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis

improves their quality of life, reduces time off school or work and improves their long-term survival.

Search strategy

We searched ClinicalTrials.gov and the Australia and New Zealand Clinical Trials Registry for relevant

trials. Date of last search: 15 March 2012.

We also searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last

search: 01 June 2012.

Selection criteria Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom

treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled

antibiotic for between one and four weeks.


Two review authors independently selected eligible trials, assessed the risk of bias in each trial and

extracted data. Authors of the included trials were contacted for more information.

Main results

Six trials with 208 participants were included in the review. Trials were heterogenous in design and

interventions (however, all included trials compared inhaled versus intravenous antibiotic regimens). Risk of

bias was difficult to assess in most trials. Results were not fully reported and only limited data were

available for analysis. Four trials reported some results on forced expiratory volume at one second and

found no significant differences between the inhaled antibiotic and the comparison intervention. In two of

these trials using 300 mg of inhaled tobramycin, the change in forced expiratory volume at one second was

similar to intravenous tobramycin; and in one trial the time until the next exacerbation was not different. No

important adverse effects were reported.


There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of

pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to

achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other

or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative

to intravenous tobramycin for some pulmonary exacerbations.



Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis

Page 5

2013 Timetable for C chrane Workshops


Nordic Cochrane Centre

For more information see: http://www.cochrane.dk/courses/index.htm

German Cochrane Centre

Dutch Cochrane Centre

For more information see: http://dcc.cochrane.org/

Australasian Cochrane Centre

Date Location Type of Workshop

07 – 09 March 2013 Freiburg Systematic Reviews in Medicine

07- 08 March 2013 Freiburg Advanced GRADE Workshop: Grading Evidence and Recommendation

08 – 09 March 2013 Freiburg GRADE Workshop: Grading Evidence and Recommendations


05 Dec – 07 Dec 2012 Sydney Introduction to writing a Cochrane review

Asia-Pacific Region Workshops

For more information see: http://acc.cochrane.org/timetable-registration


06 – 08 May 2013 Cape Town African Cochrane Indaba: Global Evidence, Local Application

Brazilian Cochrane Centre

For more information see: http://www.centrocochranedobrasil.org.br/

Canadian Cochrane Centre

Iberoamerican Cochrane Centre

For more information see: http://www.cochrane.es/


01 - 03 May 2013 St. John's, NL Cochrane Standard Author Training

South African Cochrane Centre

UK Cochrane Centre


22 Jan 2013 Oxford Workshop RA1 Beginning a Systematic Review Protocol

23 Jan 2013 Oxford Workshop RA2 The Methods Section of the Protocol

US Cochrane Centre


06 – 18 Jan 2013 Baltimore Workshop on Developing a Cochrane Systematic Review

http://www.cochrane.dk/courses/index.htm

http://dcc.cochrane.org/

C chrane Centres

Centres share a responsibility for helping to co-ordinate and support the Cochrane Collaboration. The shared

responsibility of the Cochrane Centres includes organising workshops, seminars and colloquia to support and

guide the development of the Cochrane Collaboration.

THE UK COCHRANE CENTRE National Instittue for Health Research

Summertown Pavilion

Middle Way

Oxford OX2 7LG

UK

E-mail:[email protected]

http://www.cochrane.co.uk

THE ITALIAN COCHRANE CENTRE Mario Negri Institute

Via La Masa 19

20156 Milano

ITALY

E-mail: [email protected]

http://www.cochrane.it

THE DUTCH COCHRANE CENTRE Academic Medical Centre

University of Amsterdam

Meibergdreef 15, J.2-221

Postbus 22700

1100 DE Amsterdam

NETHERLANDS


http://www.cochrane.nl

THE CANADIAN COCHRANE CENTRE Institute of Population Health

University of Ottawa

1 Stewart Street

Ottawa Ontario K1N 6N5

Canada


http://www.ccnc.cochrane.org

THE AUSTRALASIAN COCHRANE CENTRE Monash Unitversity, The Alfred Centre

99 Commercial Road

Melbourne VIC 3004

AUSTRALIA


http://acc.cochrane.org/

THE CHINESE COCHRANE CENTRE West China Hospital , Sichuan University

No 37, Guo Xue Xiang

610041 Chengdu

Sichuan

PEOPLE’S REPUBLIC OF CHINA

E-mail [email protected]

http://www.ebm.org.cn

THE GERMAN COCHRANE CENTRE Abteilung Medizinische Biometrie und Statistik

Universitaetsklinik Freiburg

Berliner Allee 29

D-79110 Freiburg in Breisgau

GERMANY


http://www.cochrane.de


THE NORDIC COCHRANE CENTRE Rigshospitalet

Blegdamsvej 9, 3343

2100 Copenhagen

DENMARK


http://www.cochrane.dk

THE BRAZILIAN COCHRANE CENTRE Universidade Federal de Sao Paulo

Rua Pedro de Toledo, 598

Sao Paulo, SP 04039-001

BRAZIL


http://www.centrocochranedobrasil.org

THE US COCHRANE CENTER Center for Clinical Trials

Johns Hopkins Bloomberg School of Public Health

615 N. Wolfe Street, Mail RM W5010

Baltimore Maryland 21205

USA


http://www.us.cochrane.org

THE SOUTH AFRICAN COCHRANE CENTRE South African Medical Research Council

PO Box 19070,

7505Tygerberg

SOUTH AFRICA


http://www.mrc.ac.za/cochrane/cochrane.htm

THE IBEROAMERICAN COCHRANE CENTRE Hospital de la Santa Creu i Sant Pau

Edifici Casa de Convalescència

Sant Antoni M. Claret 171

08041-Barcelona

SPAIN


http://www.cochrane.es/

THE FRENCH COCHRANE CENTRE Centre d'Epidémiolgie Clinique

Hôpital Hôtel-Dieu

1, place du Parvis Notre-Dame

75004 Paris FRANCE


http://www.fr.cochrane.org

THE SOUTH ASIAN COCHRANE CENTRE Evidence Informed Health Care

Christian Medical College, Carman Block II Floor

CMC Campus, Bagayam

632002 Vellore, Tamil Nadu

INDIA


http://www.cochrane-sacn.org

mailto:[email protected]





http://www.cochrane.co.uk/










http://www.cochrane.it/






http://www.cochrane.nl/









http://www.ccnc.cochrane.org/






















http://www.ebm.org.cn/












http://www.cochrane.de/








http://www.cochrane.dk/

http://www.cochrane.dk/


http://www.centrocochranedobrasil.org/



http://www.us.cochrane.org/


http://www.mrc.ac.za/cochrane/cochrane.htm












http://www.fr.cochrane.org/









http://www.cochrane-sacn.org/



- Contact Details -

Please photocopy, complete and return the following section if :

- Your contact details have changed & you wish to be kept informed about the Cystic Fibrosis

and Genetic Disorders Group

- You are not on our mailing list and you would like to receive information about the Group in the future

- You would like to be removed from the Group’s mailing list

Name :

Job title / position :

Address :

Telephone :

Fax :

E-mail address :

Proposed contribution to Cystic Fibrosis and Genetic Disorders Group, if any (e.g. undertaking a

review (give interested area) , hand searching, refereeing, etc) :

I would like to receive future mailings: Yes / No


September 1995 Registered with the Cochrane Collaboration as the Cystic Fibrosis Group

December 1997 Scope of group expanded to include other genetic diseases

Editorial Base: Cochrane Cystic Fibrosis And Genetic Disorders Group

Institute of Child Health, Alder Hey Foundation Trust

Eaton Road

Liverpool L12 2AP

Phone: +44 (0)151 252 5696

Fax: +44 (0)151 252 5456

Managing Editor (ME): Tracey Remmington E-mail: [email protected]

Assistant ME: Nikki Jahnke E-mail: [email protected]

Trials Search Co-ordinator: Natalie Yates

Medical Statistician: Dr Kerry Dwan

Co-ordinating Editor: Prof Alan Smyth (UK)

Editors: Dr Kofi Anie (UK) Dr Samir Ballas (USA)

Dr Heather Elphick (UK) Prof Ian Hambleton (Barbados)

Dr Alfonso Iorio (Italy) Prof Felix Ratjen (Canada)

Dr Karen Robinson (USA) Prof Ros Smyth (UK)

Dr Kevin Southern (UK) Dr John Walter (UK)

A/Prof Peter Wark (Australia)

Editors Emeritus: Prof Deborah Ashby (UK) Dame Prof Sally Davies (UK)

Dr Gerard Ryan (Australia)

Group Website: http://www.cfgd.cochrane.org

Current funding: NHS NIHR National Programme, UK

Trial Registers

The register of randomised controlled trials (RCTs) for cystic fibrosis contains 1963 references to

1141 RCTs. This is compiled from electronic searches of the Cochrane Central Register of Controlled

Trials (updated each new issue), quarterly searches of MEDLINE, a search of EMBASE to 1995 and

the prospective handsearching of two journals: Pediatric Pulmonology; and the Journal of Cystic

Fibrosis. Unpublished work is identified by searching the abstract books of three major cystic fibrosis

conferences: the International Cystic Fibrosis Conference; the European Cystic Fibrosis Conference

and the North American Cystic Fibrosis Conference.

The haemoglobinopathies register holds 658 references to 337 trials, the coagulopathies register

has 276 references to 196 trials, and there are also 150 references for phenylketonuria and 663

references for hyperlipoproteinaemia (subsets on the inborn errors of metabolism register). As

well as the electronic searching described above the following are searched for trials to include in the

genetic disorders registers: the journals: Haemophilia and the Journal of Inherited Metabolic Disease;

and the proceedings of the European Haematology Association conference; the American Society of

Hematology conference; the Caribbean Health Research Council Meetings; the National Sickle Cell

Disease Program Annual Meeting; the European Haematology Association conference; the American

Society of Hematology conference; and the Society for the Study of Inborn Errors of Metabolism

conference.


Cochrane Cystic Fibrosis and Genetic Disorders Group Summary sheet (November 2012)

For information on subscribing to The Cochrane Library please visit:

http://www.wileyeurope.com/go/cochrane

Output of the CFGD Group on The Cochrane Library (Issue 12, 2012)

Cystic fibrosis reviews

Active cycle of breathing technique for cystic fibrosis

Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis

Antibiotic treatment for Burkholderia cepacia complex in people with cystic fibrosis experiencing a pulmonary

exacerbation

Antibiotic treatment for non-tuberculous mycobacteria lung infection in people with CF

Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis

Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis -related arthritis

Antioxidant micronutrients for inflammation and oxidation in cystic fibrosis lung disease

Bisphosphonates for osteoporosis in people with cystic fibrosis

Chemical pleurodesis versus surgical intervention for persistent and recurrent pneumothoraces in cystic fibrosis

Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis

Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas

aeruginosa in cystic fibrosis

Conventional chest physiotherapy compared to any form of chest physiotherapy for cystic fibrosis

Disease modifying anti-rheumatic drugs in people with cystic fibrosis -related arthritis

Dornase alfa for cystic fibrosis

Drug therapies for reducing gastric acidity in cystic fibrosis

Duration of IV antibiotic therapy for people with cystic fibrosis

Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis

Enteral tube feeding for cystic fibrosis

Home intravenous antibiotics for cystic fibrosis

Inhaled antibiotics for pulmonary exacerbations in people with cystic fibrosis

Inhaled bronchodilators for cystic fibrosis

Inhaled corticosteroids for cystic fibrosis

Inspiratory muscle training for cystic fibrosis

Insulin and oral agents for managing cystic fibrosis-related diabetes

Macrolide antibiotics for cystic fibrosis

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis

Nebulised anti-pseudomonal antibiotic therapy for cystic fibrosis

Nebulised hypertonic saline for cystic fibrosis

Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis

Newborn screening for cystic fibrosis

Non-invasive ventilation for cystic fibrosis

Omega-3 fatty acids for cystic fibrosis

Once daily versus multiple daily dosing with intravenous aminoglycosides for cystic fibrosis

Oral anti-pseudomonal antibiotics for cystic fibrosis

Oral calorie supplements for cystic fibrosis

Oral non-steroidal anti-inflammatory drugs for cystic fibrosis

Oral steroids for cystic fibrosis

Oscillating devices for airway clearance in people with CF

Oxygen therapy for cystic fibrosis

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis

PEP physiotherapy for airway clearance in cystic fibrosis

Percutaneous long lines for administering intravenous antibiotics in people with cystic fibrosis

Physical training for cystic fibrosis

Pneumococcal vaccines for cystic fibrosis

Prophylactic anti-staphylococcal antibiotics for cystic fibrosis

Psychological interventions for people with cystic fibrosis and their families

Self-management education for cystic fibrosis

Singing for children and adults with cystic fibrosis

Single versus combination intravenous antibiotic therapy for people with cystic fibrosis

Sodium channel blockers for cystic fibrosis

Standard versus biofilm antimicrobial susceptibility testing for infection of Pseudomonas aeruginosa in cystic fibrosis

Timing of dornase alfa inhalation for cystic fibrosis

Timing of hypertonic saline inhalation in cystic fibrosis






Cystic fibrosis reviews (continued)

Topical cystic fibrosis transmembrane conductance regulator gene replacement for CF-related lung disease

Topical nasal steroids for treating nasal polyposis in people with cystic fibrosis

Totally implantable vascular access devices for cystic fibrosis

Ursodeoxycholic acid for cystic fibrosis -related liver disease

Vaccines for preventing infection with Pseudomonas aeruginosa in people with cystic fibrosis

Vaccines for preventing influenza in people with cystic fibrosis

Vitamin A supplementation for CF

Vitamin D supplementation for cystic fibrosis

Vitamin K supplementation for cystic fibrosis

Cystic fibrosis protocols

Appetite stimulants for people with cystic fibrosis

Autogenic drainage for CF

Bronchoscopy-guided therapy for CF

Eradication therapy for Burkholderia cepacia complex (BCC) in people with cystic fibrosis

Immunosuppressive drug therapy to prevent rejection following lung transplantation for cystic fibrosis

Inhaled mannitol for cystic fibrosis

Interventions for the eradication of methicillin resistant Staphyloccocus aureus in people with CF

Interventions for promoting physical activity in people with cystic fibrosis

Intravenous antibiotics for pulmonary exacerbations in people with CF

Nebuliser devices for drug delivery in cystic fibrosis

Pancreatic enzyme replacement therapy for people with cystic fibrosis

Recombinant growth hormone therapy for children and young adults with cystic fibrosis

Cystic fibrosis transmembrane conductance regulator correctors for cystic fibrosis

Vitamin E supplementation for cystic fibrosis

Haemoglobinopathy reviews

Antibiotics for treating acute chest syndrome in people with sickle cell disease

Antibiotics for treating community acquired pneumonia in people with sickle cell disease

Antibiotics for treating osteomyelitis in people with sickle cell disease

Blood transfusion for acute chest syndrome in people with sickle cell disease

Blood transfusion for preventing stroke in people with sickle cell disease

Deferasirox for iron chelation in people with transfusion-dependent sickle cell disease

Deferasirox for iron chelation in people with transfusion-dependent thalassaemia

Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent

thalassaemia

Drugs for preventing red blood cell dehydration in people with sickle cell disease

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease

Gene therapy for sickle cell disease

Hematopoietic stem cell transplantation for children with sickle cell disease

Hydroxyurea for sickle cell disease

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease

Inhaled nitric oxide for treating acute chest syndrome in people with sickle cell disease

Interventions for treating leg ulcers in people with sickle cell disease

Neonatal screening for sickle cell disease

Oral deferiprone for iron chelation in people with thalassaemia

Phytomedicines (medicines derived from plants) for sickle cell disease

Piracetam for reducing the incidence of sickle cell disease crises

Pneumococcal vaccines for sickle cell disease

Preoperative blood transfusions for sickle cell disease

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease

Psychological therapies to sickle cell disease and pain

Psychological therapies for thalassaemia

Regular long-term red blood cell transfusions for chronic chest complications in sickle cell disease

Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease

Stem cell transplantation for people with beta thalassaemia major

Treatment for avascular necrosis of bone in people with sickle cell disease






Haemoglobinopathy reviews (continued)

Treatments for priapism in boys and men with sickle cell disease

Vaccines for preventing invasive salmonella infections in people with sickle cell disease

Haemoglobinopathy protocols

Angiotensin-converting enzyme (ACE) inhibitors for proteinuria in people with sickle cell disease

LMWHs for managing vaso-occlusive crises in people with sickle cell disease

Zinc supplementation for thalassaemia and sickle cell disease

Coagulopathy reviews

Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A

or B

Recombinant Factor VIIa concentrate versus plasma derived concentrates for the acute treatment of Haemophilia A

& inhibitors

Coagulopathy protocols

Desmopressin acetate (DDAVP) for preventing acute bleeds during pregnancy in women with congenital bleeding

disorders

Treatment for preventing bleeding in people with congenital bleeding disorders undergoing surgery

Inborn errors of metabolism reviews

Bisphosphonate therapy for osteogenesis imperfecta

Carnitine supplementation for the treatment of inborn errors of metabolism

Dietary interventions for phenylketonuria

Dietary treatment for familial hypercholesterolaemia

Enzyme replacement therapy for Fabry disease

Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome)

Hematopoietic stem cell transplantation for Gaucher disease

Newborn screening for homocystinuria

Protein substitute for children and adults with phenylketonuria

Recombinant growth hormone therapy for X-linked hypophosphatemia in children

Sapropterin dihydrochloride for phenylketonuria

Statins for familial hypercholesterolemia in children

Tyrosine supplementation in phenylketonuria

Inborn errors of metabolism protocols

Enzyme replacement therapy with laronidase (Aldurazyme®) for treating mucopolysaccharidosis type I

Orphan reviews

Dietary advice for illness-related malnutrition in adults

Embolisation therapy for pulmonary arteriovenous malformations

Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung

disease

Oral protein calorie supplementation for children with chronic disease

Pycnogenol® for the treatment of chronic disorders

Orphan protocols

Surgical interventions for treating pectus excavatum



Documents

Cochrane Cystic Fibrosis & Genetic Disorders Group...Cochrane Cystic Fibrosis and Genetic Disorders Review Group Page 2 Methodological Expectations of Cochrane Intervention Reviews