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Single versus combination intravenous antibiotic therapy for people with cystic fibrosis.

BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in CF requires further evaluation. OBJECTIVES: To assess the effectiveness of single compared to combination intravenous antibiotic therapy for treating people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search of the Group's register: January 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a single intravenous antibiotic with a combination of that antibiotic plus a second antibiotic in people with CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Twenty-seven trials were identified, of which eight trials (with 356 participants) comparing a single agent to a combination of the same antibiotic and one other, were included. There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups. There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures. These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor. AUTHORS' CONCLUSIONS: The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.

Aminoglycosides↗

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

BACKGROUND: Patients with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require repeated courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher concentrations less often. OBJECTIVES: To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. SEARCH STRATEGY: We searched the Cystic Fibrosis specialist trials register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: February 2000. SELECTION CRITERIA: All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy and/or toxicity, in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality. Authors of one study were contacted to obtain missing information. MAIN RESULTS: Two trials reporting results from a total of 70 patients were included in this review. Both trials compared once-daily dosing with thrice-daily dosing reporting data on Forced Expiratory Volume at one second (FEV1), Forced Vital Capacity (FVC), nutritional status and side effects. There was no significant difference in efficacy or in the incidence of ototoxicity and nephrotoxicity between treatment groups. REVIEWER'S CONCLUSIONS: Despite a lack of difference between the two groups we feel that these results should be viewed with caution as the numbers of patients involved was small and lacks the power to detect a difference between the groups. This systematic review has highlighted the need for a well designed, adequately-powered, multicentre, randomised controlled trial assessing the efficacy of once-daily versus multiple-daily dosing of intravenous aminoglycosides for pulmonary exacerbations in cystic fibrosis.

Adolescent↗

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

BACKGROUND: People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. OBJECTIVES: To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. SEARCH STRATEGY: We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: August 2005. SELECTION CRITERIA: All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy and/or toxicity, in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The two authors independently selected the studies to be included in the review and assessed methodological quality of each study. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. MAIN RESULTS: Eleven studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants were included in this review. All studies compared once-daily dosing with thrice-daily dosing. There was no significant difference between treatment groups in: forced expiratory volume at one second, weighted mean difference (WMD) 0.33 (95% confidence interval (CI) -2.81 to 3.48); forced vital capacity, WMD 0.29 (95% CI -6.58 to 7.16); % weight for height, WMD -0.82 (95% CI -3.77 to 2.13); body mass index, WMD 0.00 (95% CI -0.42 to 0.42); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96). The percentage change in creatinine significantly favoured once-daily treatment in children, WMD -8.20 (95% CI -15.32 to -1.08), but showed no difference in adults, WMD 3.25 (95% CI -1.82 to 8.33). AUTHORS' CONCLUSIONS: Once and three times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.

Adolescent↗

Bisphosphonates for osteoporosis in people with cystic fibrosis.

BACKGROUND: Osteoporosis is a disorder of bone mineralization that can lead to reduced bone mineral density and an increased risk for fractures. It is found in about one third of adults with cystic fibrosis. Bisphosphonates have been shown to increase bone mineral density and decrease the risk of new fractures in post-menopausal women and in patients receiving long-term oral corticosteroids. OBJECTIVES: To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, study withdrawals, and survival in people with cystic fibrosis. SEARCH STRATEGY: Relevant trials were identified in the Cochrane Cystic Fibrosis and Genetic Disorders Review Group specialised register of controlled trials by the centre co-ordinator. This register comprises references identified from comprehensive electronic database searches, handsearching of relevant journals and of conference proceedings. Additional sources such as abstract books for osteoporosis conferences were hand-searched by the authors. The most recent search(es) were conducted in February 2001. SELECTION CRITERIA: Randomised controlled trials of at least six months duration that studied the use of bisphosphonates in adults with cystic fibrosis were considered for inclusion. Outcomes included one of the following: fractures, bone mineral density, quality of life, adverse events, study withdrawals, or survival. DATA COLLECTION AND ANALYSIS: Information on study design, participants, interventions, and outcomes was abstracted from included studies. Two independent reviewers abstracted the information. Authors were contacted to obtain missing data. MAIN RESULTS: Two trials were identified in the trials search. Both trials with a total of 65 participants were included in this review. One study examined patients without lung transplants while the other study included only patients who had received a lung transplant. The intervention in both trials was pamidronate administered intravenously every three months. In patients who had not received a lung transplant, bone mineral density at axial sites was increased after six months of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change BMD] = 5.8 [95% CI 4.63 to 6.97], hip WMD = 3.00 [95% CI 1.99 to 4.01]). There was a small decrease in forearm bone mineral density in patients treated with pamidronate versus controls (distal forearm WMD = -1.70 [95% CI -2.46 to -0.94]). Bone pain was the most common adverse event occurring in 11/15 participants not using corticosteroids (RR = 24.40, 95% CI 1.57 to 381.48). There was no difference in survival (RR = 1.00, 95% CI 0.83 to 1.20), although this may be due to short follow-up and small sample size. In patients who had received a lung transplant, the number of new fractures did not change with the use of pamidronate (non-vertebral RR = 3.38 [95% CI 0.39 to 29.29], vertebral RR = 0.56 [95% CI 0.17 to 1.89]). Bone mineral density at axial sites was increased after two years of treatment in the treatment group compared to the control group (lumbar spine WMD [for % change in BMD] = 6.20 [95% CI 4.28 to 8.12], femur WMD = 7.90 [95% CI 5.78 to 10.03]). REVIEWER'S CONCLUSIONS: Intravenous pamidronate increases bone mineral density at axial sites in people with cystic fibrosis, although it can cause severe bone pain in patients not receiving corticosteroids. Additional studies in larger populations are needed to determine the effect on fracture rate and survival.

Bone Density↗

Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited life-limiting disorder, characterised by pulmonary infections and thick airway secretions. Chest physiotherapy has been integral to clinical management in facilitating removal of airway secretions. Conventional chest physiotherapy techniques (CCPT) have depended upon assistance during treatments, while more contemporary airway clearance techniques are self-administered, facilitating independence and flexibility. OBJECTIVES: To compare CCPT with other airway clearance techniques in terms of their effects on respiratory function, individual preference, adherence, quality of life and other outcomes. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched CINAHL from 1982 to 2002 and AMED from 1985 to 2002. Date of most recent search: January 2004. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials including those with a cross-over design where CCPT was compared with other airway clearance techniques. Studies of less than seven days duration were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers allocated quality scores to relevant studies and independently extracted data. If we were unable to extract data, we invited authors to submit their data. We excluded studies from meta-analysis when data were lost or study design precluded comparison. For some continuous outcomes, we used the generic inverse variance method for meta-analysis of data from cross-over trials and data from parallel-designed trials were incorporated for comparison. We also examined efficacy of specific techniques and effects of treatment duration. MAIN RESULTS: Seventy-eight publications were identified by the searches. Twenty-nine of these were included, representing 15 data sets with 475 participants. There was no difference between CCPT and other airway clearance techniques in terms of respiratory function measured by standard lung function tests. Studies undertaken during acute exacerbations demonstrated relatively large gains in respiratory function irrespective of airway clearance technique. Longer-term studies demonstrated smaller improvements or deterioration over time. Ten studies reported individual preferences for technique, with participants tending to favour self-administered techniques. Heterogeneity in the measurement of preference precluded these data from meta-analysis. AUTHORS' CONCLUSIONS: This review demonstrated no advantage of CCPT over other airway clearance techniques in terms of respiratory function. There was a trend for participants to prefer self-administered airway clearance techniques. Limitations of this review included a paucity of well-designed, adequately-powered, long-term trials.

Cystic Fibrosis↗

Multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working age adults.

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for chronic low back pain patients. The biopsychosocial approach for low back pain could also be considered to prevent chronicity by carrying out the rehabilitation if the acute pain is prolonged. Nevertheless multidisciplinary treatment programmes are often laborious and long processes and require good collaboration between the patient, the rehabilitation team and the work place. By workplace visits and close relationship with occupational health care one might expect results in terms of patients working ability. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for subacute low back pain among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on subacute low back pain were separated afterwards. SELECTION CRITERIA: From all references found in our original search we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of multidisciplinary rehabilitation for working age patients suffering from subacute low back pain (more than 4 weeks but less than 3 months). The rehabilitation program was required to be multidisciplinary, i.e.; it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the randomized controlled trials and controlled trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only 2 relevant studies that satisfied our criteria on subacute low back pain. They were both considered to be methodologically low quality randomized controlled trials. The clinical relevance of included studies was sufficient. The level of scientific evidence for the effectiveness of multidisciplinary rehabilitation was moderate on subacute low back pain showing that multidisciplinary rehabilitation which includes workplace visit or more comprehensive occupational health care intervention helps patients to return to work faster, makes sick leaves less and alleviates subjective disability. REVIEWER'S CONCLUSIONS: We conclude that there is moderate evidence of positive effectiveness of multidisciplinary rehabilitation for subacute low back pain and workplace visit increases the effectiveness. But because this evidence is based on the trials that had some methodological shortcomings and several expensive multidisciplinary rehabilitation programmes are commonly used for common subacute low back problems, there is an obvious need for high quality trials in this field.

Acute Disease↗

Multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults.

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs for neck and shoulder pain require substantial staff and financial resources. Despite questionable scientific evidence of their effectiveness, they are widely used. Neck and shoulder complaints are common among working age adults and they are often associated with physical work load and stress. Pain in the neck and shoulder area cause biopsychosocial difficulties for the patient especially if disability due to pain is prolonged. To help patients with biopsychosocial problems or to prevent their development, multidisciplinary biopsychosocial programs are applied on rehabilitation for neck and shoulder pain patients. Nevertheless multidisciplinary treatment programmes are often laborious and rather long processes and require good collaboration between the patient, the rehabilitation team and the work place. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on neck and shoulder pain were separated afterwards. SELECTION CRITERIA: From all references found in our original search we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of biopsychosocial rehabilitation for patients suffering from neck and shoulder pain among working age adults. The rehabilitation program was required to be multidisciplinary, i.e.; it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the randomized controlled trials and controlled trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only 2 relevant studies that satisfied our criteria. One of these was considered methodologically low quality randomized controlled trial and the other one was a methodologically low quality controlled clinical trial. The clinical relevance of included studies was satisfactory. The level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation was limited for neck and shoulder pain. REVIEWER'S CONCLUSIONS: We conclude that there appears to be little scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation compared with other rehabilitation facilities on neck and shoulder pain. Multidisciplinary rehabilitation is a commonly used intervention for chronic neck and shoulder complaints, therefore we see an urgent need for high quality trials in this field.

Adult↗

Omega-3 fatty acids (from fish oils) for cystic fibrosis.

BACKGROUND: Epidemiological (population studies) and other studies suggest that a diet rich in omega-3 essential fatty acids (derived from fish oil) may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. OBJECTIVES: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality. To identify any adverse events associated with omega-3 polyunsaturated fatty acid supplementation. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialised trials register, which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Authors and persons interested in the question were contacted. Date of the most recent search of the Group's specialised register: May 2002. SELECTION CRITERIA: Randomised controlled trials in patients with cystic fibrosis in which omega-3 fatty acid supplements were compared with a placebo oil. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials to be included in the review and assessed the methodological quality of the trials using two approaches: Cochrane assessment of allocation concealment and Jadad quality assessment score. Using data acquisition forms, two reviewers independently extracted data. Missing data has been requested. MAIN RESULTS: The initial literature search identified six trials. Two trials, involving 31 participants satisfied our inclusion criteria and were included in the review. Both compared omega-3 fatty acids to olive oil controls for a six week treatment period. One study (19 participants) showed an improvement in FEV1, FVC, Shwachman score and reduction in sputum volume in the fish oil group at the end of this short treatment period. REVIEWER'S CONCLUSIONS: The review of trials found that regular omega-3 supplements may provide some benefits for people with cystic fibrosis with relatively few adverse effects, although the evidence is insufficient to draw firm conclusions. There is insufficient evidence to recommend routine use of supplements of omega-3 fatty acids in people with cystic fibrosis. The most notable feature highlighted by this review was the lack of data for many of the outcomes likely to be meaningful to people with or making treatment decisions about CF. A large, long-term, multi-centre, randomised controlled study is needed in order to determine if there is a significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes.

Cystic Fibrosis↗

Hydroxyurea for sickle cell disease.

BACKGROUND: Sickle cell disease is one of the most common inherited diseases world wide. It is associated with life long morbidity and a reduced life expectancy. Hydroxyurea, a chemotherapeutic drug taken by mouth, raises fetal haemoglobin and, as such, is expected to ameliorate some of the clinical problems of sickle cell disease. OBJECTIVES: To assess the effects of hydroxyurea therapy in sickle cell disease patients of all types, of any age, regardless of setting. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialised register of controlled trials for haemoglobinopathies, which comprises references identified from comprehensive electronic database searches, hand-searching relevant journals, and hand-searching abstract books of conference proceedings. Date of the most recent search(es): November 2000. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing the use of oral hydroxyurea for one month or longer with placebo, standard therapy or other interventions for the treatment of patients with sickle cell disease. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and extracted data from the two studies included. MAIN RESULTS: Twenty trials were found of which two trials, which reported results from a total of 324 adults and children were suitable for inclusion in the review. From the data provided in the published reports only one study (the MSH study to the United States of America) could be analysed. This study showed marked differences in favour of hydroxyurea treatment as compared with placebo in terms of annual crisis rate, use of transfusions, and life-threatening complications (in particular, the acute sickle chest syndrome). No serious adverse effects were reported from either study. REVIEWER'S CONCLUSIONS: While hydroxyurea appears both effective and safe in the severely affected SS adults over a two year period; further studies are required to elucidate its role in other patient groups and for other conditions.

Antisickling Agents↗

Macrolide antibiotics for cystic fibrosis.

BACKGROUND: Chronic severe infection with Pseudomonas aeruginosa, affects many people with cystic fibrosis (CF). There is evidence from the laboratory and from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this organism. OBJECTIVES: We aimed to test the hypotheses that, in people with CF, macrolide antibiotics:(1) improve clinical status compared to placebo or another antibiotic;(2) do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture macrolide antibiotics for unpublished or follow-up data (December 2003). Most recent search of the Group's register: January 2004 SELECTION CRITERIA: Published or unpublished randomised controlled trials of macrolide antibiotics compared to placebo, another class of antibiotic or another macrolide antibiotic. Studies comparing regimens of the same macrolide antibiotic at different doses will also be included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. Three groups were contacted for missing data and we hope to include these in future reviews. MAIN RESULTS: Searches identified 14 studies, four were included in this review (296 participants). Two studies enrolled adults, one children (a significant number of whom were not colonised with Pseudomonas aeruginosa) and one both adults and children. All the clinical studies reported small but significant improvements in respiratory function with azithromycin versus placebo. Meta-analysis at the one-month and six-month time points demonstrates a significant benefit with respect to relative change in FEV1 (at six months, for n = 104, azithromycin and n = 114, placebo; WMD 5.82% (95% CI 2.45 to 9.20)). The largest study reported a significant increase in mild adverse events (nausea, diarrhoea and wheezing). REVIEWERS' CONCLUSIONS: There is clear evidence from these studies of a small but significant improvement in respiratory function following treatment with azithromycin. The largest study employed a three times a week dose and, in this study, treatment with azithromycin was associated with a significant increase in mild adverse events. Further studies are needed to clarify the precise role of azithromycin in the treatment of CF lung disease.

Anti-Bacterial Agents↗

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Allergic Bronchopulmonary Aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. Corticosteroids, in high doses, are the main treatment for ABPA although the long-term benefits are not clear and their many side effects are well documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, Itraconazole is the most active. A separate antifungal compound, Amphotericin B has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. OBJECTIVES: The review tested the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects. If benefit was demonstrated, the optimal type, duration and dose of antifungal therapy was assessed. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. In addition, pharmaceutical companies were approached. SELECTION CRITERIA: Randomised controlled trials, published or unpublished, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: No completed randomised controlled trials were identified. MAIN RESULTS: No completed randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Adult↗

Biopsychosocial rehabilitation for upper limb repetitive strain injuries in working age adults.

BACKGROUND: Upper limb repetitive strain injury is a common problem in western countries, causing human suffering and huge economical losses. Patients with prolonged pain associated with repetitive tasks in the work place can face both psychological and physical difficulties. Different treatment programmes, physical, psychological, behavioural, social and occupational treatments have been developed and used to help these patients. OBJECTIVES: The objective of this systematic review is to determine the effectiveness of biopsychosocial rehabilitation for upper limb repetitive strain injuries among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for a more broad area of musculoskeletal disorders. Trials on repetitive strain injuries were separated afterwards. SELECTION CRITERIA: Randomised controlled trials and controlled trials comparing biopsychosocial measures for the treatment of repetitive upper limb strain injury in working age adults DATA COLLECTION AND ANALYSIS: Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of biopsychosocial rehabilitation. MAIN RESULTS: We found only two relevant studies that satisfied our criteria. They assessed the effectiveness of two specific interventions and were both considered as low quality trials. The clinical relevance of the included studies was also unsatisfactory. The level of scientific evidence for the effectiveness of biopsychosocial rehabilitation for repetitive strain injuries was limited. One small trial found that hypnosis supplementary to comprehensive treatment can decrease the intensity of pain for acute RSI in six weeks follow-up. REVIEWER'S CONCLUSIONS: We conclude that presently there appears to be little scientific evidence for the effectiveness of biopsychosocial rehabilitation on repetitive strain injuries. As RCTs on more intensive and comprehensive biopsychosocial treatment programmes for RSI are lacking, there does not seem to be reliable data for these interventions. There is a need for high quality trials in this field.

Adult↗

Chinese herbal medicine for atopic eczema.

BACKGROUND: Traditional Chinese herbal mixtures have been used to treat atopic eczema for many years. Their efficacy has attracted public attention and recently some clinical trials have been undertaken. OBJECTIVES: To assess the effects of Chinese herbal mixtures in the treatment of atopic eczema. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( January 2004), the Cochrane Skin Group Specialised Register (January 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), CINHL (1980 to January 2004) and a number of complementary medicine databases. In addition, the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in oral traditional Chinese herbs and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials of Chinese herbal mixtures used in the treatment of atopic eczema. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed the quality of the trials and extracted data. Any discrepancies were discussed to achieve consensus. MAIN RESULTS: Four randomised controlled trials, with eight weeks for each phase, met the inclusion criteria. The trials randomised 159 participants aged from 1 to 60 years. The withdrawal rates ranged from 7.5% to 22.5% and no trial used intention to treat analysis. Three trials were randomised placebo controlled, two-phase cross-over designs assessing the same Chinese herbal mixture, Zemaphyte. In two of these three trials the reduction in erythema and surface damage was greater on Zemaphyte than on placebo, and participants slept better and itched less and expressed a preference for Zemaphyte. The fourth trial was an open-label design comparing Zemaphyte in herbal form with Zemaphyte as a freeze dried preparation. There was a reduction in erythema and surface damage with both formulations, but no comparison between the two formulations was reported. Some adverse effects were reported in all four trials, but none were regarded as serious. REVIEWERS' CONCLUSIONS: Chinese herbal mixtures may be effective in the treatment of atopic eczema. However, only four small poorly reported RCTs of the same product, Zemaphyte, were found and the results were heterogeneous. Further well-designed, larger scale trials are required, but Zemaphyte is no longer being manufactured.

Dermatitis, Atopic↗

Chinese herbal medicine for atopic eczema.

BACKGROUND: Traditional Chinese herbal mixtures have been used to treat atopic eczema for many years. Their efficacy has attracted public attention and recently some clinical trials have been undertaken. OBJECTIVES: To assess the effects of Chinese herbal mixtures in the treatment of atopic eczema. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( January 2004), the Cochrane Skin Group Specialised Register (January 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), CINHL (1980 to January 2004) and a number of complementary medicine databases. In addition, the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in oral traditional Chinese herbs and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials of Chinese herbal mixtures used in the treatment of atopic eczema. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed the quality of the trials and extracted data. Any discrepancies were discussed to achieve consensus. MAIN RESULTS: Four randomised controlled trials, with eight weeks for each phase, met the inclusion criteria. The trials randomised 159 participants aged from 1 to 60 years. The withdrawal rates ranged from 7.5% to 22.5% and no trial used intention to treat analysis. Three trials were randomised placebo controlled, two-phase cross-over designs assessing the same Chinese herbal mixture, Zemaphyte. In two of these three trials the reduction in erythema and surface damage was greater on Zemaphyte than on placebo, and participants slept better and expressed a preference for Zemaphyte. One trial also reported that participants itched less. The fourth trial was an open-label design comparing Zemaphyte in herbal form with Zemaphyte as a freeze dried preparation. There was a reduction in erythema and surface damage with both formulations, but no comparison between the two formulations was reported. Some adverse effects were reported in all four trials, but none were regarded as serious. AUTHORS' CONCLUSIONS: Chinese herbal mixtures may be effective in the treatment of atopic eczema. However, only four small poorly reported RCTs of the same product, Zemaphyte, were found and the results were heterogeneous. Further well-designed, larger scale trials are required, but Zemaphyte is no longer being manufactured.

Dermatitis, Atopic↗

Nitrates for achalasia.

BACKGROUND: Achalasia is a disease that impairs oesophageal motility. Though nitrates have been used to treat achalasia for a long time, the effectiveness of nitrates for achalasia is still controversial. OBJECTIVES: To quantify short-term and long-term effects of nitrate therapy in patients with achalasia. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 4-2001), MEDLINE (1966-2001), EMBASE (1980-2001), LILACS - Latin American and Caribbean health science literature (1982-2001) and CBM-Chinese Biomedical database(1980-2000). Additionally, all references in the identified trials were checked for further relevant trials. SELECTION CRITERIA: All randomised controlled trials involving achalasic patients given any type of nitrates were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent observers based on the intention to treat principle. MAIN RESULTS: Two randomised cross-over studies were found, but no results are included. Due to the design of the studies and the method of reporting the results in the original paper it was not possible to extract the necessary information to examine any of the outcomes. REVIEWER'S CONCLUSIONS: We can conclude no implications for practice at this stage. Appropriately designed parallel group randomised controlled trials with long term follow-up are needed to determine the effects of nitrates.

Esophageal Achalasia↗

Nitrates for achalasia.

BACKGROUND: Achalasia is a disease that impairs oesophageal motility. Though nitrates have been used to treat achalasia for a long time, the effectiveness of nitrates for achalasia is still controversial. OBJECTIVES: To quantify short-term and long-term effects of nitrate therapy in patients with achalasia. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 4-2001), MEDLINE (1966-2001), EMBASE (1980-2001), LILACS - Latin American and Caribbean health science literature (1982-2001) and CBM-Chinese Biomedical database(1980-2000). Additionally, all references in the identified trials were checked for further relevant trials. An updated search was run on the Cochrane Library, MEDLINE, and EMBASE in September 2003 - no new trials were found. SELECTION CRITERIA: All randomised controlled trials involving achalasic patients given any type of nitrates were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent observers based on the intention to treat principle. MAIN RESULTS: Two randomised cross-over studies were found, but no results are included. Due to the design of the studies and the method of reporting the results in the original paper it was not possible to extract the necessary information to examine any of the outcomes. REVIEWER'S CONCLUSIONS: We can conclude no implications for practice at this stage. Appropriately designed parallel group randomised controlled trials with long term follow-up are needed to determine the effects of nitrates.

Esophageal Achalasia↗

Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis.

BACKGROUND: Pseudomonas aeruginosa is the commonest micro-organism associated with respiratory infections in cystic fibrosis. Retrospective studies have suggested that survival is increased by using an aggressive policy of intravenous antipseudomonal antibiotics at regular intervals, irrespective of symptoms. OBJECTIVES: To determine whether there is evidence that an elective (regular) versus symptomatic intravenous antibiotic regime is associated with an improvement in clinical status and survival rates in patients with cystic fibrosis. To identify any adverse effects associated with the use of elective intravenous antibiotics, including an increase in the development of resistant organisms. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetics Disorders Group Specialist Trials Register was used. This comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstracts from conference proceedings. Date of the most recent search of the Group's specialised register: October 2000. SELECTION CRITERIA: All randomised or pseudo-randomised controlled trials describing the use of elective compared with symptomatic intravenous antibiotic policies for any duration or dose regimen. Elective versus symptomatic intravenous antibiotic regimes against any organisms were considered. Patients with cystic fibrosis were of any age or disease severity. DATA COLLECTION AND ANALYSIS: Trials were independently assessed for inclusion criteria, methodological quality and data extraction by the two reviewers. MAIN RESULTS: Three trials were identified by the initial search. Two trials reporting results from a total of 79 patients were included in the review. Differences in study design and objectives meant that data could not be pooled for meta-analysis. Neither trial demonstrated significant differences in outcome measures between intervention and comparison groups. REVIEWER'S CONCLUSIONS: Studies are insufficient to identify conclusive evidence favouring a policy of elective intravenous antibiotic administration, despite its widespread use. Neither are the potential risks adequately evaluated. The results should be viewed with caution as patient numbers are small. Clearly there is a need for a well-designed, adequately powered, multi-centred randomised controlled trial to evaluate these issues.

Anti-Bacterial Agents↗

Physical training for cystic fibrosis.

BACKGROUND: Physical training may form an important part of the care package for patients with cystic fibrosis. OBJECTIVES: To determine whether a prescribed regime of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: August 2001. SELECTION CRITERIA: All randomised controlled clinical trials in which a prescribed regime of physical training is compared to no physical training in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed methodological quality and extracted data. MAIN RESULTS: Of the sixteen trials identified six trials, which included 184 patients, met the inclusion criteria. Exercise tolerance in the short term, during an acute admission was improved in patients who received physical training. In a three year study there was no improvement in exercise tolerance at the end of the study period. Over three years there was a significantly greater mean annual rate of decline in FVC in the control group compared to the exercise group WMD 2.17 (95%CI 0.47, 3.87). Changes in other lung function parameters showed a similar trend, but these were not statistically significant. REVIEWER'S CONCLUSIONS: Conclusions about the efficacy of physical training in cystic fibrosis are limited by the small size, short duration and incomplete reporting of most of the trials included in this review. Physical training is already part of the care package offered to most patients with cystic fibrosis and there is no evidence to actively discourage this. Further research is needed to assess comprehensively the net benefit of the addition of physical training to the care of cystic fibrosis patients.

Cystic Fibrosis↗