| { |
| "PICO": { |
| "P": "\"Cystic Fibrosis\" AND \"Cystic Fibrosis Pulmonary Exacerbation\" AND (\"Infant\" OR \"Child\" OR \"Adult\" OR \"Aged\")", |
| "I": "\"Intravenous\" AND \"Antibiotic Therapy\"", |
| "C": "\"Placebo\" OR (\"Antibiotic Therapy\" AND (\"Intravenous\" OR \"Nebulised\" OR \"Nebulizer\" OR \"Oral\"))", |
| "O": "\"Forced Expiratory Volume 1\" OR \"Forced Vital Capacity\" OR \"Lung function test\" OR \"Chronic Respiratory Infection Symptom Score\" OR \"Cystic Fibrosis Questionnaire-Revised\" OR \"Quality of Life\" OR \"Time-to-Event\" OR \"Cystic Fibrosis Pulmonary Exacerbation\"", |
| "S": "Randomised controlled trials (RCTs) and the first treatment cycle of cross-over studies", |
| "Details": { |
| "P Details": "INCLUSION: Cystic fibrosis diagnosed by accepted consensus criteria AND pulmonary exacerbation/acute respiratory worsening explicitly targeted for IV antibiotic treatment AND randomised trial population; all ages OR any lung disease stage were eligible. Population boundary in included studies commonly involved pulmonary exacerbations with chronic OR acute Pseudomonas aeruginosa lung/respiratory infection.; EXCLUSION: Quasi-randomised populations OR participants not treated for pulmonary exacerbation in both arms OR studies without an IV antibiotic comparator OR studies exclusively comparing different dose levels/pharmacokinetics/toxicity of the same antibiotic OR crossover studies without first-period data OR mixed populations where CF data were not separable/insufficiently predominant.", |
| "I Details": "INCLUSION: Randomised controlled trials OR first treatment cycle of cross-over studies AND people with cystic fibrosis experiencing a pulmonary exacerbation AND a study explicitly aiming to trial IV antibiotics for treatment AND comparison of a single IV antibiotic regimen versus a combination IV antibiotic regimen, with or without placebo support in one arm; EXCLUSION: Studies exclusively comparing different dose levels of the same antibiotic OR quasi-randomised studies OR studies without an IV antibiotic comparator OR studies not treating pulmonary exacerbations in both arms OR cross-over studies without first-arm data", |
| "O Details": "INCLUSION: Randomised controlled trials OR first treatment cycle of cross-over trials in people with cystic fibrosis experiencing a pulmonary exacerbation AND explicitly evaluating IV antibiotics AND reporting at least one prespecified effectiveness/safety outcome: FEV1 change OR FVC change OR symptom score using a validated tool OR time to next exacerbation OR quality of life OR nutritional status (BMI OR weight) OR mortality OR adverse effects/toxicity OR microbiological resistance.; EXCLUSION: Studies with no outcomes relevant to the review OR reporting outcomes only in non-usable forms without extractable data for the review analyses/narrative summaries; additionally excluded were studies not treating pulmonary exacerbations in both arms, studies without an IV antibiotic comparator, and studies limited to dosing/pharmacokinetic/toxicity questions without the review’s clinical effectiveness outcomes." |
| } |
| }, |
| "trials": [ |
| { |
| "relation_type": "include", |
| "pmid": "2508049", |
| "has_rob": "True", |
| "study name": "De Boeck 1989" |
| }, |
| { |
| "relation_type": "include", |
| "pmid": "7019407", |
| "has_rob": "True", |
| "study name": "Hyatt 1981" |
| }, |
| { |
| "relation_type": "include", |
| "pmid": "3906545", |
| "has_rob": "True", |
| "study name": "Macfarlane 1985" |
| }, |
| { |
| "relation_type": "include", |
| "pmid": "3393383", |
| "has_rob": "True", |
| "study name": "McCarty 1988" |
| }, |
| { |
| "relation_type": "include", |
| "pmid": "10190914", |
| "has_rob": "True", |
| "study name": "Smith 1999" |
| } |
| ], |
| "study group": [ |
| { |
| "group num": "5.13", |
| "outcome": "Adverse effects. Details: Adverse effects of IV antibiotic treatment, including toxicity/allergy (e.g. ototoxicity, nephrotoxicity, kidney injury, idiosyncratic reactions, raised liver/renal blood markers, gastrointestinal or haematological events) and microbiological resistance/new resistant strains; generally analysed as number of participants with events.", |
| "study arm": "Single intravenous (IV) antibiotic (no placebo) versus combination IV antibiotic. Details: Intervention: single active IV antibiotic regimen alone; Control: combination regimen of two active IV antibiotics.", |
| "Subgroup": "Rash. Details: Adverse-effect subgroup for incidence of rash in the comparison of a single IV antibiotic versus a combination of two IV antibiotics. Intervention: single IV antibiotic regimen; control: two-IV-antibiotic combination regimen.", |
| "Data type": "Dichotomous", |
| "Effect measure": "Odds Ratio", |
| "data_studies": "McCarty 1988" |
| }, |
| { |
| "group num": "6.1", |
| "outcome": "FEV1 (all measures). Details: Lung function measured as forced expiratory volume in 1 second (FEV1), assessed as absolute and/or relative change from baseline to end of therapy; reported variably as % predicted (%) or absolute volume (L or mL).", |
| "study arm": "Single versus combination intravenous (IV) antibiotic regimens. Details: Intervention: single-agent IV antibiotic regimen (including single active IV antibiotic plus placebo in some trials); Control: combination IV antibiotic regimen with two or more active antibiotics.", |
| "Subgroup": "Single antibiotic plus placebo versus combination regimen. Details: Subgroup within the review comparison 'single intravenous antibiotic versus combination intravenous antibiotic', specifically trials where the single-agent arm was created by adding placebo to the background regimen. Intervention: single active IV antibiotic plus placebo; control: active combination IV antibiotic regimen.", |
| "Data type": "Continuous", |
| "Effect measure": "Std. Mean Difference", |
| "data_studies": "Hyatt 1981,Macfarlane 1985,Smith 1999", |
| "gt conclusion": "not significant" |
| }, |
| { |
| "group num": "6.1", |
| "outcome": "FEV1 (all measures). Details: Lung function measured as forced expiratory volume in 1 second (FEV1), assessed as absolute and/or relative change from baseline to end of therapy; reported variably as % predicted (%) or absolute volume (L or mL).", |
| "study arm": "Single versus combination intravenous (IV) antibiotic regimens. Details: Intervention: single-agent IV antibiotic regimen (including single active IV antibiotic plus placebo in some trials); Control: combination IV antibiotic regimen with two or more active antibiotics.", |
| "Subgroup": "Single antibiotic (no placebo) versus combination regimen. Details: Subgroup within the review comparison 'single intravenous antibiotic versus combination intravenous antibiotic', specifically trials comparing a true single active IV antibiotic alone against a two-drug IV combination, without placebo used to mimic combination therapy. Intervention: single active IV antibiotic alone; control: active two-IV-antibiotic combination regimen.", |
| "Data type": "Continuous", |
| "Effect measure": "Std. Mean Difference", |
| "data_studies": "De Boeck 1989" |
| }, |
| { |
| "group num": "6.7", |
| "outcome": "FVC (all measures). Details: Lung function measured as forced vital capacity (FVC), assessed as absolute and/or relative change from baseline to end of therapy; reported variably as % predicted (%) or absolute volume (L or mL).", |
| "study arm": "Single versus combination intravenous (IV) antibiotic regimens. Details: Intervention: single-agent IV antibiotic regimen (including single active IV antibiotic plus placebo in some trials); Control: combination IV antibiotic regimen with two or more active antibiotics.", |
| "Subgroup": "Single antibiotic with placebo versus combination regimen. Details: Same subgroup concept as 'single antibiotic plus placebo versus combination regimen': studies in which the single-agent arm included placebo to match the combination regimen. Intervention: single active IV antibiotic with placebo; control: active combination IV antibiotic regimen.", |
| "Data type": "Continuous", |
| "Effect measure": "Std. Mean Difference", |
| "data_studies": "Hyatt 1981,Smith 1999", |
| "gt conclusion": "not significant" |
| } |
| ], |
| "De Boeck 1989": [ |
| { |
| "group num": "6.1", |
| "Analysis group": "6", |
| "Analysis number": "1", |
| "Subgroup": "Single antibiotic (no placebo) versus combination regimen", |
| "Experimental mean": "16.0", |
| "Experimental SD": "11.75", |
| "Experimental cases": "", |
| "Experimental N": "11", |
| "Control mean": "15.0", |
| "Control SD": "11.28", |
| "Control cases": "", |
| "Control N": "10", |
| "Mean": "0.083263", |
| "CI start": "-0.773563", |
| "CI end": "0.940088" |
| }, |
| { |
| "RoB": "1.0", |
| "Domain1：Random sequence generation (selection bias)": "Unclear", |
| "Domain2：Allocation concealment (selection bias)": "Unclear", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes": "Unclear", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes": "Low", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes": "Low", |
| "Domain6：Selective reporting (reporting bias)": "Unclear", |
| "Domain1：Random sequence generation (selection bias) Support for judgement": "Randomisation stated but not described.", |
| "Domain2：Allocation concealment (selection bias) Support for judgement": "No information given.", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes Support for judgement": "Participants and clinicians were not blinded but this may not have affected the outcomes as they were objective measurements of lung function, time to next exacerbation, mortality and weight.", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes Support for judgement": "Lung function undertaken by a technician blinded to regimen.", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes Support for judgement": "No withdrawals.", |
| "Domain6：Selective reporting (reporting bias) Support for judgement": "None identified." |
| } |
| ], |
| "Hyatt 1981": [ |
| { |
| "group num": "6.1", |
| "Analysis group": "6", |
| "Analysis number": "1", |
| "Subgroup": "Single antibiotic plus placebo versus combination regimen", |
| "Experimental mean": "3.67", |
| "Experimental SD": "5.81", |
| "Experimental cases": "", |
| "Experimental N": "9", |
| "Control mean": "13.21", |
| "Control SD": "9.92", |
| "Control cases": "", |
| "Control N": "14", |
| "Mean": "-1.070527", |
| "CI start": "-1.974246", |
| "CI end": "-0.166809" |
| }, |
| { |
| "group num": "6.7", |
| "Analysis group": "6", |
| "Analysis number": "7", |
| "Subgroup": "Single antibiotic with placebo versus combination regimen", |
| "Experimental mean": "5.89", |
| "Experimental SD": "11.69", |
| "Experimental cases": "", |
| "Experimental N": "9", |
| "Control mean": "15.21", |
| "Control SD": "13.86", |
| "Control cases": "", |
| "Control N": "14", |
| "Mean": "-0.687001", |
| "CI start": "-1.552322", |
| "CI end": "0.17832" |
| }, |
| { |
| "RoB": "1.0", |
| "Domain1：Random sequence generation (selection bias)": "Low", |
| "Domain2：Allocation concealment (selection bias)": "Low", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes": "Low", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes": "Low", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes": "Low", |
| "Domain6：Selective reporting (reporting bias)": "Unclear", |
| "Domain1：Random sequence generation (selection bias) Support for judgement": "Randomly assigned using a table of random numbers.", |
| "Domain2：Allocation concealment (selection bias) Support for judgement": "Antibiotics and placebo were prepared in pharmacy and delivered in coded bottles. Code was not broken in case of 'treatment failure'.", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes Support for judgement": "Described as 'double‐blind'. Antibiotics and placebo were prepared in pharmacy and delivered in coded bottles. Code was not broken in case of 'treatment failure'. Sham serum levels of sisomicin given by (unblinded) pharmacists.", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes Support for judgement": "Described as 'double‐blind' with parents, participants and clinicians blinded as above.", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes Support for judgement": "In the case that participants were removed from the study due to \"early failure\" (control 3/9; treatment 2/15) the data from the last day of study participation contributed to the data analysis.", |
| "Domain6：Selective reporting (reporting bias) Support for judgement": "Insufficient data." |
| } |
| ], |
| "Macfarlane 1985": [ |
| { |
| "group num": "6.1", |
| "Analysis group": "6", |
| "Analysis number": "1", |
| "Subgroup": "Single antibiotic plus placebo versus combination regimen", |
| "Experimental mean": "9.75", |
| "Experimental SD": "9.7", |
| "Experimental cases": "", |
| "Experimental N": "4", |
| "Control mean": "1.8", |
| "Control SD": "15.7", |
| "Control cases": "", |
| "Control N": "5", |
| "Mean": "0.525006", |
| "CI start": "-0.828982", |
| "CI end": "1.878995" |
| }, |
| { |
| "RoB": "1.0", |
| "Domain1：Random sequence generation (selection bias)": "Unclear", |
| "Domain2：Allocation concealment (selection bias)": "Unclear", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes": "Low", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes": "Low", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes": "High", |
| "Domain6：Selective reporting (reporting bias)": "Unclear", |
| "Domain1：Random sequence generation (selection bias) Support for judgement": "Described as randomly assigned but no method given.", |
| "Domain2：Allocation concealment (selection bias) Support for judgement": "No method described.", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes Support for judgement": "Described as double‐blind. Identities of infusions known only to pharmacy personnel.", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes Support for judgement": "Described as double‐blind.", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes Support for judgement": "2 participants withdrew and did not contribute data to the analysis.", |
| "Domain6：Selective reporting (reporting bias) Support for judgement": "Insufficient information." |
| } |
| ], |
| "McCarty 1988": [ |
| { |
| "group num": "5.13", |
| "Analysis group": "5", |
| "Analysis number": "13", |
| "Subgroup": "Rash", |
| "Experimental mean": "", |
| "Experimental SD": "", |
| "Experimental cases": "0", |
| "Experimental N": "8", |
| "Control mean": "", |
| "Control SD": "", |
| "Control cases": "1", |
| "Control N": "9", |
| "Mean": "0.333333", |
| "CI start": "0.011826", |
| "CI end": "9.395344" |
| }, |
| { |
| "RoB": "1.0", |
| "Domain1：Random sequence generation (selection bias)": "Unclear", |
| "Domain2：Allocation concealment (selection bias)": "Low", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes": "Unclear", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes": "Unclear", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes": "Low", |
| "Domain6：Selective reporting (reporting bias)": "Unclear", |
| "Domain1：Random sequence generation (selection bias) Support for judgement": "Described as randomly assigned but no details given.", |
| "Domain2：Allocation concealment (selection bias) Support for judgement": "Sequentially numbered envelopes were used, although it is not clear if these were opaque and sealed. On balance, considered low risk.", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes Support for judgement": "Unblinded but this is unlikely to affect objective outcomes such as lung function, microbiology, mortality and weight. It may have an effect for subjective outcomes such as adverse events. We have therefore graded the risk of bias as unclear.", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes Support for judgement": "Unblinded but this is unlikely to affect the measurement of objective outcomes such as lung function, microbiology and weight. It may have an effect for measurement of subjective outcomes such as adverse events. We have therefore graded the risk of bias as unclear.", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes Support for judgement": "No withdrawals.", |
| "Domain6：Selective reporting (reporting bias) Support for judgement": "Insufficient information." |
| } |
| ], |
| "Smith 1999": [ |
| { |
| "group num": "6.1", |
| "Analysis group": "6", |
| "Analysis number": "1", |
| "Subgroup": "Single antibiotic plus placebo versus combination regimen", |
| "Experimental mean": "12.7", |
| "Experimental SD": "6.86", |
| "Experimental cases": "", |
| "Experimental N": "30", |
| "Control mean": "11.6", |
| "Control SD": "7.27", |
| "Control cases": "", |
| "Control N": "36", |
| "Mean": "0.153384", |
| "CI start": "-0.331883", |
| "CI end": "0.638651" |
| }, |
| { |
| "group num": "6.7", |
| "Analysis group": "6", |
| "Analysis number": "7", |
| "Subgroup": "Single antibiotic with placebo versus combination regimen", |
| "Experimental mean": "15.3", |
| "Experimental SD": "12.15", |
| "Experimental cases": "", |
| "Experimental N": "36", |
| "Control mean": "15.4", |
| "Control SD": "12.36", |
| "Control cases": "", |
| "Control N": "30", |
| "Mean": "-0.00807", |
| "CI start": "-0.492588", |
| "CI end": "0.476448" |
| }, |
| { |
| "RoB": "1.0", |
| "Domain1：Random sequence generation (selection bias)": "Low", |
| "Domain2：Allocation concealment (selection bias)": "Unclear", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes": "Low", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes": "Low", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes": "High", |
| "Domain6：Selective reporting (reporting bias)": "Unclear", |
| "Domain1：Random sequence generation (selection bias) Support for judgement": "Randomised by the core centre pharmacist with a code generated at that centre.", |
| "Domain2：Allocation concealment (selection bias) Support for judgement": "Not stated.", |
| "Domain3：Blinding of participants and personnel (performance bias) All outcomes Support for judgement": "Described as placebo‐controlled double‐blind with unblinded third parties adjusting tobramycin dosages and dummy adjusting placebo dosages by study pharmacist.", |
| "Domain4：Blinding of outcome assessment (detection bias) All outcomes Support for judgement": "Blinded.", |
| "Domain5：Incomplete outcome data (attrition bias) All outcomes Support for judgement": "35 withdrawals were described, although not analysed as ITT.", |
| "Domain6：Selective reporting (reporting bias) Support for judgement": "Insufficient information." |
| } |
| ], |
| "date": "2023/12" |
| } |
|
|
