***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature

***DOCUMENTATION***

***EXAMPLES***

Input: We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results. The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants). Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality. Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants). Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia. The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests. We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes. This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter. Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.
Output:

We searched for studies up to May 2017, and we included four studies involving a total of 495 people with interstitial lung disease due to connective tissue disease. Some people were given cyclophosphamide, and others were given other drugs or a placebo. We compared these different groups to look for differences. We found some low-quality evidence showing small benefit of using cyclophosphamide compared with placebo in terms of lung function and symptoms of breathlessness. No clear evidence shows that people who took cyclophosphamide had better lung function than people who took a different drug (mycophenolate mofetil). Some people experienced low blood counts, blood in their urine, and nausea. We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. A rating of very low-quality evidence means that we are uncertain about the results. A rating of high-quality evidence means that we are very certain about the results. For this Cochrane review, we found evidence of low quality. We included randomised controlled trials that were blinded, which means that participants and those people who assessed study results did not know whether participants had received cyclophosphamide or a placebo. However, the trials mostly included people with systemic sclerosis, so these results may not apply to all people with interstitial lung disease with connective tissue disease.