Rituximab for treating inhibitors in people with inherited severe hemophilia.

BACKGROUND: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. DATA COLLECTION AND ANALYSIS: No randomized controlled trials matching the selection criteria were eligible for inclusion. MAIN RESULTS: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified. AUTHORS' CONCLUSIONS: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis.

OBJECTIVE: To determine the comparative efficacy and safety of corticosteroids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants. STUDY DESIGN: We systematically searched PubMed, EMBASE and the Cochrane Library. Two reviewers independently selected randomised controlled trials (RCTs) of postnatal corticosteroids in preterm infants. A Bayesian network meta-analysis and subgroup analyses were performed. RESULTS: We included 47 RCTs with 6747 participants. The use of dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.29, 95% credible interval (CrI) 0.14 to 0.52; OR 0.58, 95% CrI 0.39 to 0.76, respectively). High-dose dexamethasone was more effective than hydrocortisone, beclomethasone and low-dose dexamethasone. Early and long-term dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.11, 95% CrI 0.02 to 0.4; OR 0.37, 95% CrI 0.16 to 0.67, respectively). There were no statistically significant differences in the risk of cerebral palsy (CP) between different corticosteroids. However, high-dose and long-term dexamethasone ranked lower than placebo and other regimens in terms of CP. Subgroup analyses indicated budesonide was associated with a decreased risk of BPD in extremely preterm and extremely low birthweight infants (OR 0.60, 95% CrI 0.36 to 0.93). CONCLUSIONS: Dexamethasone can reduce the risk of BPD in preterm infants. Of the different dexamethasone regimens, aggressive initiation seems beneficial, while a combination of high-dose and long-term use should be avoided because of the possible adverse neurodevelopmental outcome. Dexamethasone and inhaled corticosteroids need to be further evaluated in large-scale RCTs with long-term follow-ups.

Rituximab for treating inhibitors in people with inherited severe hemophilia.

BACKGROUND: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 16 February 2017. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. DATA COLLECTION AND ANALYSIS: No randomized controlled trials matching the selection criteria were eligible for inclusion. MAIN RESULTS: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified. AUTHORS' CONCLUSIONS: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis.

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (-32.80, -14.18), P < 0.00001], 7day [MD: -33.01, 95% CI (-37.31, -28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P < 0.00001], as well as the duration of phototherapy [MD: -0.64, 95% CI (-0.84, -0.44), P < 0.00001] and hospitalization [MD: -2.68, 95% CI (-3.18, -2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice.

Development of indicators for assessing rational drug use to treat community-acquired pneumonia in children in hospitals and clinics: A modified Delphi study.

Community-acquired pneumonia (CAP) is a common infectious disease in children. Rational drug use (RDU) is an important approach to reducing the disease burden and mortality rate of CAP in children. There are no monitoring indicators for assessing RDU in children. This study aimed to develop a set of indicators to assess RDU to treat CAP in children in hospitals and clinics using a modified Delphi method.Initial indicators were generated based on a systematic review of guidelines and studies investigating CAP in children. A 3-round modified Delphi process in the form of an email survey combined with round-table discussion was then carried out, and an analytic hierarchy process (AHP) was applied to determine the weight of each indicator.A total of 24 and 8 experts were invited to participate in the email survey and round-table discussion, respectively. A consensus was reached after 3 rounds of the Delphi survey. Three first-rank indicators and 23 second-rank indicators were developed, and each indicator was weighted. The first-rank indicators comprised drug choice (45.5%), drug usage and dosage (36.4%), and the duration of drug therapy (18.2%); the second-rank indicators were indicators related to antibiotics (63.6%), antiviral agents (18.2%), traditional Chinese medicines (4.5%), and adjuvant drugs (13.6%). The weight value of drug selection was the highest, followed by the values of drug usage and dosage and the duration of drug therapy.The developed indicator set constitutes the first set intended to assess RDU to treat CAP in children in hospitals (including community hospitals) and clinics. The indicators were based on drug selection, drug usage and dosage and duration of drug therapy, which are associated with most therapeutic drugs for CAP in children. Monitoring these indicators will guide people towards the promotion of RDU in the absence of drug monitoring indicators for CAP. Furthermore, the indicator set constitutes a methodological reference for the development of other indicator sets.

Cisplatin for testicular germ cell tumors: a rapid review.

OBJECTIVE: Cisplatin is one of efficacious medicines for TGCT, but is not in 18th WHO EML now. The Union for International Cancer Control recommended cisplatin to the 19th WHO EML for TGCT. To evaluate the effectiveness, safety and cost of cisplatin for TGCT according to the requirements of WHO EML Expert Committee, and to provide the evidence whether cisplatin should be included in WHO EML. METHOD: We searched The Cochrane Library, PubMed, EMbase, NHS EED, US National Guideline Clearinghouse (NGC) and WHO guidelines. Guidelines and systematic reviews (SRs) on cisplatin for TGCT were included. Two reviewers selected studies and extracted relevant information independently. Quality of SRs was appraised through AMSTAR. RESULTS: Seven guidelines and four SRs were included in this rapid review. Quality of SRs was moderate according to AMSTAR. The results showed that: (a) effectiveness: cisplatin-based chemotherapy significantly improved in response rates and overall survival for more advanced disease (stage II and stage III). Bleomycin, etoposide, and cisplatin (BEP)-one of the most widely used of cisplatin-based chemotherapy regimens should be considered as the standard treatment of good-prognosis patients with survival rates of 90% and as the best option for intermediate- or poor-prognosis patients with survival rates of 75% and 50%, respectively. (b) Safety: nephrotoxicity, ototoxicity and peripheral neuropathy are common adverse effects of cisplatin. (c) Cost: there was no relevant study about cost of cisplatin for TGCT. But the affordability of cispaltin is good for Chinese patients, due to it is in health insurance directory of China. CONCLUSIONS: We recommend cisplatin to be listed in 19th WHO EML for TGCT, due to adequate evidence of effectiveness and good affordability.