Cochrane Db Syst Rev
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Cochrane Db Syst Rev · Aug 2018
ReviewCorrectors (specific therapies for class II CFTR mutations) for cystic fibrosis.
Cystic fibrosis (CF) is a common life-shortening condition caused by mutation in the gene that codes for that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a salt transporter. F508del, the most common CFTR mutation that causes CF, is found in up to 80% to 90% of people with CF. In people with this mutation, a full length of protein is transcribed, but recognised as misfolded by the cell and degraded before reaching the cell membrane, where it needs to be positioned to effect transepithelial salt transport. This severe mutation is associated with no meaningful CFTR function. A corrective therapy for this mutation could positively impact on an important proportion of the CF population. ⋯ There is insufficient evidence that monotherapy with correctors has clinically important effects in people with CF who have two copies of the F508del mutation.Combination therapies (lumacaftor-ivacaftor and tezacaftor-ivacaftor) each result in similarly small improvements in clinical outcomes in people with CF; specifically improvements quality of life (moderate-quality evidence), in respiratory function (high-quality evidence) and lower pulmonary exacerbation rates (moderate-quality evidence). Lumacaftor-ivacaftor is associated with an increase in early transient shortness of breath and longer-term increases in blood pressure (high-quality evidence). These adverse effects were not observed for tezacaftor-ivacaftor. Tezacaftor-ivacaftor has a better safety profile, although data are not available for children younger than 12 years. In this age group, lumacaftor-ivacaftor had an important impact on respiratory function with no apparent immediate safety concerns, but this should be balanced against the increase in blood pressure and shortness of breath seen in longer-term data in adults when considering this combination for use in young people with CF.
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Cochrane Db Syst Rev · Aug 2018
Meta AnalysisRed blood cell transfusion to treat or prevent complications in sickle cell disease: an overview of Cochrane reviews.
Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Red blood cell (RBC) transfusions are used to treat complications of SCD, e.g. acute chest syndrome (ACS) (this often involves a single transfusion episode), or they can be part of a regular long-term transfusion programme to prevent SCD complications. ⋯ This overview provides support from two high-quality Cochrane Reviews for the use of RBC transfusions in preventing stroke in children and adolescents at high risk of stroke (abnormal TCDs or SCI) and evidence that it may decrease the risk of SCI in children with abnormal TCD velocities. In addition RBC transfusions may reduce the risk of ACS and painful crisis in this population.This overview highlights the lack of high-quality evidence in adults with SCD and the number of reviews that have no evidence for the use of RBC transfusions across a spectrum of SCD complications. Also of concern is the variable and often incomplete reporting of patient-relevant outcomes in the included trials such as SCD-related serious adverse events and quality of life.
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Cochrane Db Syst Rev · Aug 2018
Meta AnalysisNatalizumab for induction of remission in Crohn's disease.
This systematic review update summarizes the current evidence on the use of natalizumab for induction of remission in Crohn's disease (CD). ⋯ High quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD. However, none of the included studies had the power to detect rare but serious adverse events such as PML. Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy. The use of natalizumab in select patients (e.g. patients allergic to different biologics) needs to be carefully considered against the potential risk of developing PML. Futher studies of natalizumab are not likely to be done.