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The Cochrane Database of Systematic... Aug 2017Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012.
OBJECTIVES
To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH METHODS
In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.
SELECTION CRITERIA
Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.
MAIN RESULTS
We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I = 0%, high-quality evidence). Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I = 0%, high-quality evidence). Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).
AUTHORS' CONCLUSIONS
Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA was more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.
Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Estradiol; Female; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Mifepristone; Norpregnadienes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Unsafe Sex
PubMed: 28766313
DOI: 10.1002/14651858.CD001324.pub5 -
Frontiers in Immunology 2023To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To present the pooled quantitative evidence of baseline characteristics and clinical outcomes of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK).
METHODS
A comprehensive systematic review and meta-analysis was performed on all available studies retrieved from the MEDLINE, Embase, and Cochrane databases, using TCZ in patients with refractory TAK. We applied the commands and in Stata Software to pool overall estimates of continuous data and binomial data, respectively. A random-effects model was recruited for analysis.
RESULTS
Nineteen studies with 466 patients were included in this meta-analysis. The mean age at implementation of TCZ was 34.32 years. Female sex and Numano Type V were the most prominent baseline characteristics. During the 12-month follow-up when receiving TCZ treatment, pooled CRP was 1.17 mg/L (95% confidence interval [CI] -0.18-2.52), pooled ESR was 3.54 mm/h (95% CI 0.51-6.58), and pooled glucocorticoid dose was 6.26 mg/d (95% CI 4.24-8.27). Approximately 76% (95% CI 58-87%) of patients achieved a decrease in glucocorticoid dosage. Meanwhile, patients with TAK had a remission rate of 79% (95% CI 69-86%), a relapse rate of 17% (95% CI 5-45%), an imaging progress rate of 16% (95% CI 9-27%), and a retention rate of 68% (95% CI 50-82%). Adverse events occurred in 16% (95% CI 5-39%) of patients, and infection was the most common adverse event, with a rate of 12% (95% CI 5-28%).
CONCLUSION
TCZ treatment can provide favorable outcomes in terms of inflammatory markers, steroid-sparing effects, clinical response, drug retention and minimizing adverse effects for patients with refractory TAK.
Topics: Humans; Female; Adult; Glucocorticoids; Takayasu Arteritis; Treatment Outcome; Antibodies, Monoclonal, Humanized
PubMed: 36845158
DOI: 10.3389/fimmu.2023.1084558 -
Acta Obstetricia Et Gynecologica... Dec 2022The objective of this study was to evaluate the association between caffeine and alcohol consumption and in vitro fertilization (IVF) and intracytoplasmic sperm... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The objective of this study was to evaluate the association between caffeine and alcohol consumption and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes.
MATERIAL AND METHODS
The protocol was registered in the PROSPERO database on May 23, 2021 (registration number: CRD42021256649), and updated on August 4, 2022. Two researchers performed a literature search in the PubMed, Embase, and MEDLINE databases for articles published before July 15, 2022 independently. Studies investigating the association between caffeine and alcohol consumption and IVF/ICSI outcomes were included, and studies reporting the consumption amount were analyzed using a one-stage robust error meta-regression-based method to explore potential dose-response relation. Funnel plot was used to assess publication bias if more than 10 studies were included.
RESULTS
Twelve studies on caffeine consumption and 14 studies on alcohol consumption were included in the systematic review, of which seven and nine were eligible for the meta-analysis. These studies included 26 922 women and/or their spouses who underwent IVF/ICSI treatment. Women's and men's caffeine consumption was not significantly associated with the pregnancy rate (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.85-1.12; OR 0.93, 95% CI 0.75-1.14; respectively) and the live birth rate (OR 0.98, 95% CI 0.89-1.08; OR 0.98, 95% CI 0.86-1.12; respectively) of IVF/ICSI. Maternal alcohol consumption was negatively associated with pregnancy after IVF/ICSI treatment (OR 0.83, 95% CI 0.69-1.01). Paternal alcohol consumption was negatively associated with partner's live birth after IVF/ICSI treatment (OR 0.88, 95% CI 0.79-0.99). Compared with abstainers, the chance of achieving a pregnancy after IVF/ICSI treatment decreased by 7% for women who consumed 84 g alcohol per week (OR 0.93, 95% CI 0.90-0.98), and the chance of partners achieving a live birth decreased by 9% for men who consumed 84 g alcohol per week (OR 0.91, 95% CI 0.88-0.94).
CONCLUSIONS
There was no association between caffeine consumption and pregnancy or live birth rate of IVF/ICSI. Women's alcohol consumption was associated with decreased pregnancy rate after IVF/ICSI treatment when weekly consumption was greater than 84 g. Men's alcohol consumption was associated with decreased live birth rate after IVF/ICSI treatment when weekly consumption was greater than 84 g.
Topics: Pregnancy; Male; Female; Humans; Sperm Injections, Intracytoplasmic; Caffeine; Semen; Pregnancy Rate; Fertilization in Vitro; Live Birth; Alcohol Drinking
PubMed: 36259227
DOI: 10.1111/aogs.14464 -
Cureus Jun 2023There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with... (Review)
Review
There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with neurotoxicity. We conducted a systematic review using online data to explore the trend of cefepime-induced neurotoxicity over the last 10 years. Forty-six articles met our inclusion criteria, including 73 cases of cefepime-induced neurotoxicity. We noticed a steady increase in the reports of cefepime-induced neurotoxicity, from one case in 2013 to 11 cases in 2022. Individuals aged 65 and older accounted for most cefepime-induced neurotoxicity cases (52%). The top three indications for cefepime administration included bone and joint infections (25%), urinary tract infections (22.7%), and pneumonia (22.7%). Most patients with renal impairment have never had a renal adjustment of their cefepime dosage (either 2 g 12 hours a day or 2 g eight hours a day). Most cases of cefepime-induced neurotoxicity occurred between days two and five (n=29, 71%), while most resolution occurred between days one and five (n=29, 85%). While cefepime continues to be a popularly used and effective antibiotic against gram-negative bacteria like , its dosage needs to be adjusted in patients with renal impairment to avoid neurotoxicity.
PubMed: 37503476
DOI: 10.7759/cureus.40980 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
Vaccines Dec 2022Considering the indeterminate effects following the administration of three doses of the SARS-CoV-2 vaccine to patients under dialysis, the present study aimed to... (Review)
Review
BACKGROUND
Considering the indeterminate effects following the administration of three doses of the SARS-CoV-2 vaccine to patients under dialysis, the present study aimed to evaluate the immunogenicity rates of patients who received the three-dose vaccine.
METHODS
MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials were searched to select the relevant literature to perform the present review. We included randomized controlled trials, non-randomized trials, prospective, observational cohort, and case-control studies to assess the humoral and cellular immune responses following the administration of the three-dose SARS-CoV-2 vaccine to patients receiving dialysis.
RESULTS
Overall, 38 studies are included in the meta-analysis presented in this paper. For patients on dialysis, the overall humoral antibody response rate is 97% following three doses of mRNA or viral vector vaccines and 100% following four doses of the SARS-CoV-2 vaccine. A subgroup analysis shows that the antibody response rate is 96% for patients on hemodialysis (HD) and 100% for those receiving peritoneal dialysis (PD). The antibody response rate in the different immunogen-vaccinated groups tends to be higher than that in the same immunogen-vaccinated group (99% vs. 96%). For those who exhibit no response following two doses of the vaccine, the third and fourth doses can elevate the antibody response rate to 81%, and that number for low responders increases to 96%. However, the pooled results obtained from the relatively few trials conducted indicate that the positive T-cell response rate only increases to 59% following three doses of the vaccine. The antibody response rate is not different between dialysis and non-dialysis groups (relative risk = 0.95, 95% CI 0.90-1.02) following three doses of the vaccine. The relative risks for a SARS-CoV-2 breakthrough infection, all-cause mortality, and hospital admissions are 0.59 (95% CI 0.30-1.04), 0.63 (95% CI 0.35-1.12), and 0.53 (95% CI 0.37-0.74), respectively, when comparing three doses with two doses of the vaccine administered to the dialysis population.
CONCLUSIONS
The third or fourth dose of the SARS-CoV-2 vaccine significantly increases the immunogenicity rates in dialysis patients, and this beneficial effect does not vary with the type of vaccine (the same or different immunogen vaccination), dialysis modality (HD or PD), or previous low response following the administration two doses of the vaccine. We believe that healthcare workers should encourage patients receiving dialysis to receive a third or fourth vaccine dose to strengthen their immunity against SARS-CoV-2.
PubMed: 36560480
DOI: 10.3390/vaccines10122070 -
Vaccines Jul 2022The emergence of breakthrough infections and new highly contagious variants of SARS-CoV-2 threaten the immunization in individuals who had completed the primary COVID-19... (Review)
Review
The emergence of breakthrough infections and new highly contagious variants of SARS-CoV-2 threaten the immunization in individuals who had completed the primary COVID-19 vaccination. This systematic review and meta-analysis investigated, for the first time, acceptance of the first COVID-19 booster dose and its associated factors among fully vaccinated individuals. We followed the PRISMA guidelines. We searched Scopus, Web of Science, Medline, PubMed, ProQuest, CINAHL and medrxiv from inception to 21 May 2022. We found 14 studies including 104,047 fully vaccinated individuals. The prevalence of individuals who intend to accept a booster was 79.0%, while the prevalence of unsure individuals was 12.6%, and the prevalence of individuals that intend to refuse a booster was 14.3%. The main predictors of willingness were older age, flu vaccination in the previous season, and confidence in COVID-19 vaccination. The most important reasons for decline were adverse reactions and discomfort experienced after previous COVID-19 vaccine doses and concerns for serious adverse reactions to COVID-19 booster doses. Considering the burden of COVID-19, a high acceptance rate of booster doses could be critical in controlling the pandemic. Our findings are innovative and could help policymakers to design and implement specific COVID-19 vaccination programs in order to decrease booster vaccine hesitancy.
PubMed: 35891260
DOI: 10.3390/vaccines10071097 -
Chinese Neurosurgical Journal Sep 2022TTFields is a novel treating modality of glioblastoma (GBM) which can significantly prolong the overall survival (OS) of newly diagnosed or recurrent glioblastoma. Some... (Review)
Review
TTFields is a novel treating modality of glioblastoma (GBM) which can significantly prolong the overall survival (OS) of newly diagnosed or recurrent glioblastoma. Some researchers have revealed that a variety of factors can affect the efficacy of TTFields. So, we review the available literature about the influencing factors on efficacy of TTFields and then choose two experimentally supported factors: the dose of dexamethasone and compliance of TTFields to perform a meta-analysis. The PubMed, Embase, and the Cochrane Library are searched. Five articles are identified between 2014 and 2017. Three articles are about the compliance of TTFields. Two articles are about the dose of dexamethasone. The Newcastle-Ottawa Quality Assessment Scale (NOS) is used as an assessment tool to evaluate the methodological quality of all included trials. The scale's range varies from 0 to 9 stars. According to the Cochrane Handbook for Systematic Reviews of Interventions, articles are graded in six items to evaluate the risk of bias. Two reviewers rate the studies independently and the final decision is reached by consensus.Our data shows that the median OS is conspicuously longer in the TTFields group in which the dose of dexamethasone is ≤ 4.1 mg, WMD = 9.23 [95% CI 5.69-12.78]; P < 0.05). And the patients whose compliance of TTFields treatment ≥ 75% (≥ 18 h per day) have a significant lower overall survival risk than the patients whose compliance of TTFields treatment < 75% (HR = 0.57 [95% CI 0.46-0.70]; P < 0.00001).TTFields is a safe and efficient novel treatment modality. The dose of dexamethasone ≤ 4.1 mg of TTFields treatment and the compliance of TTFields treatment ≥ 75%, ≥ 18 h per day are beneficial to the prognosis of the glioblastoma patients.
PubMed: 36056409
DOI: 10.1186/s41016-022-00294-0 -
The Cochrane Database of Systematic... Mar 2016This is an update of the Cochrane review "Teriflunomide for multiple sclerosis" (first published in The Cochrane Library 2012, Issue 12).Multiple sclerosis (MS) is a... (Review)
Review
BACKGROUND
This is an update of the Cochrane review "Teriflunomide for multiple sclerosis" (first published in The Cochrane Library 2012, Issue 12).Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. It is clinically characterized by recurrent relapses or progression, or both, often leading to severe neurological disability and a serious decline in quality of life. Disease-modifying therapies (DMTs) for MS aim to prevent occurrence of relapses and disability progression. Teriflunomide is a pyrimidine synthesis inhibitor approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a DMT for adults with relapsing-remitting MS (RRMS).
OBJECTIVES
To assess the absolute and comparative effectiveness and safety of teriflunomide as monotherapy or combination therapy versus placebo or other disease-modifying drugs (DMDs) (interferon beta (IFNβ), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, dimethyl fumarate, alemtuzumab) for modifying the disease course in people with MS.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Specialised Trials Register (30 September 2015). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to September 2015) from the MS societies in Europe and America. We also communicated with investigators participating in trials of teriflunomide and the pharmaceutical company, Sanofi-Aventis.
SELECTION CRITERIA
We included randomized, controlled, parallel-group clinical trials with a length of follow-up of one year or greater evaluating teriflunomide, as monotherapy or combination therapy, versus placebo or other approved DMDs for people with MS without restrictions regarding dose, administration frequency and duration of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures of Cochrane. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. We contacted the principal investigators of included studies for additional data or confirmation of data.
MAIN RESULTS
Five studies involving 3231 people evaluated the efficacy and safety of teriflunomide 7 mg and 14 mg, alone or with add-on IFNβ, versus placebo or IFNβ-1a for adults with relapsing forms of MS and an entry Expanded Disability Status Scale score of less than 5.5.Overall, there were obvious clinical heterogeneities due to diversities in study designs or interventions and methodological heterogeneities across studies. All studies had a high risk of detection bias for relapse assessment and a high risk of bias due to conflicts of interest. Among them, three studies additionally had a high risk of attrition bias due to a high dropout rate and two studies had an unclear risk of attrition bias. The studies of combination therapy with IFNβ (650 participants) and the study with IFNβ-1a as controls (324 participants) also had a high risk for performance bias and a lack of power due to the limited sample.Two studies evaluated the benefit and the safety of teriflunomide as monotherapy versus placebo over a period of one year (1169 participants) or two years (1088 participants). A meta-analysis was not conducted. Compared to placebo, administration of teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduced the number of participants with at least one relapse over one year (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.59 to 0.87, P value = 0.001 with 7 mg/day and RR 0.60, 95% CI 0.48 to 0.75, P value < 0.00001 with 14 mg/day) or two years (RR 0.85, 95% CI 0.74 to 0.98, P value = 0.03 with 7 mg/day and RR 0.80, 95% CI 0.69 to 0.93, P value = 0.004 with 14 days). Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression over one year (RR 0.55, 95% CI 0.36 to 0.84, P value = 0.006) or two years (RR 0.74, 95% CI 0.56 to 0.96, P value = 0.02). When taking the effect of drop-outs into consideration, the likely-case scenario analyses still showed a benefit in reducing the number of participants with at least one relapse, but not for the number of participants with disability progression. Both doses also reduced the annualized relapse rate and the number of gadolinium-enhancing T1-weighted lesions over two years. Quality of evidence for relapse outcomes at one year or at two years was low, while for disability progression at one year or at two years was very low.When compared to IFNβ-1a, teriflunomide at a dose of 14 mg/day had a similar efficacy to IFNβ-1a in reducing the proportion of participants with at least one relapse over one year, while teriflunomide at a dose of 7 mg/day was inferior to IFNβ-1a (RR 1.52, 95% CI 0.87 to 2.67, P value = 0.14; 215 participants with 14 mg/day and RR 2.74, 95% CI 1.66 to 4.53, P value < 0.0001; 213 participants with 7 mg/day). However, the quality of evidence was very low.In terms of safety profile, the most common adverse events associated with teriflunomide were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse events had a dose-related effects and rarely led to treatment discontinuation.
AUTHORS' CONCLUSIONS
There was low-quality evidence to support that teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduces both the number of participants with at least one relapse and the annualized relapse rate over one year or two years of treatment in comparison with placebo. Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression and delayed the progression of disability over one year or two years, but the quality of the evidence was very low. The quality of available data was too low to evaluate the benefit teriflunomide as monotherapy versus IFNβ-1a or as combination therapy with IFNβ. The common adverse effects were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse effects were mostly mild-to-moderate in severity, but had a dose-related effect. New studies of high quality and longer follow-up are needed to evaluate the comparative benefit of teriflunomide on these outcomes and the safety in comparison with other DMTs.
Topics: Adult; Crotonates; Humans; Hydroxybutyrates; Immunologic Factors; Immunosuppressive Agents; Interferon-beta; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Nitriles; Randomized Controlled Trials as Topic; Toluidines; Young Adult
PubMed: 27003123
DOI: 10.1002/14651858.CD009882.pub3 -
Movement Disorders Clinical Practice 2016This systematic review was performed to elucidate dosing practices, dosing conversions, and related outcomes from randomized controlled trials that directly compared...
OBJECTIVE
This systematic review was performed to elucidate dosing practices, dosing conversions, and related outcomes from randomized controlled trials that directly compared onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO) at various dose conversion ratios for therapeutic use in movement disorders.
METHODS
A systematic review of 3 medical literature databases (PubMed, the Cochrane Library, and EMBASE) was performed to identify relevant comparative clinical studies, systematic reviews, and meta-analyses published in the English language between January 1991 and January 2015. Studies that met predefined inclusion criteria were selected for formal data extraction and quality assessment.
RESULTS
A total of 182 manuscripts were identified, of which 4 were included for analysis. Targeted clinical applications included neurological disorders. The studies compared ONA to ABO dose conversion ratios of 1:2.5 (n=1), 1:3 (n=2), and 1:4 (n=2). One study compared both 1:3 and 1:4 ratios. An ONA:ABO conversion factor of 1:2.5 was associated with similar efficacy and side effects. An ONA:ABO ratio of 1:3 provided similar or higher efficacy but an increased rate of adverse effects, and an ONA:ABO ratio of 1:4 was associated with higher efficacy but with an excessive rate of intolerable side effects.
CONCLUSION
A dose conversion ratio of ONA to ABO between 1:2.5 and 1:3.0 provides comparable safety and efficacy for therapeutic movement disorders chemodenervation procedures.
PubMed: 27110585
DOI: 10.1002/mdc3.12235