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The Cochrane Database of Systematic... Aug 2018Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011.
OBJECTIVES
To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events.
DATA COLLECTION AND ANALYSIS
One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach.
MAIN RESULTS
We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children.
AUTHORS' CONCLUSIONS
Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.
Topics: Adolescent; Beclomethasone; Betamethasone; Budesonide; Child; Child, Preschool; Croup; Dexamethasone; Epinephrine; Fluticasone; Glucocorticoids; Humans; Infant; Infant, Newborn; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 30133690
DOI: 10.1002/14651858.CD001955.pub4 -
Malaria Journal Jul 2017Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia.
METHODS
A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p < 0.10 and I > 50.
RESULTS
Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1-96.6), p < 0.001, I = 98.39% was noticed. However, treatment success was higher in falciparum malaria patients treated with artemether-lumefantrine than chloroquine for Plasmodium vivax patients [98.1% (97.0-99.2), p < 0.001, I = 72.55 vs 94.7% (92.6-96.2), p < 0.001, I = 53.62%]. Seven studies reported the adverse drug reactions to anti-malarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1-65.5), p = 0.002.
CONCLUSIONS
On the basis of this review, anti-malarial treatment success was high (92.9%) and standard regimens showed good efficacy against Plasmodium falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Drug Combinations; Ethanolamines; Ethiopia; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Primaquine; Pyrimethamine; Sulfadoxine; Treatment Failure
PubMed: 28673348
DOI: 10.1186/s12936-017-1922-9 -
Neurology India 2022Current recommendations prescribe either nicardipine or labetalol as the first-line treatment for acute hypertension due to ease of use, availability, and low price.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Current recommendations prescribe either nicardipine or labetalol as the first-line treatment for acute hypertension due to ease of use, availability, and low price. However, it is unclear if these drugs have different effectiveness and safety profiles. This systematic review and meta-analysis aimed to compare the efficacy and safety of labetalol and nicardipine in patients with acute stroke.
MATERIALS AND METHODS
MEDLINE via PubMed, Scopus, Embase, and Google Scholar databases were electronically searched for the eligible publications from inception until March 2022. All full-text journal papers in English which compared the efficacy of nicardipine with that of labetalol on lowering blood pressure (BP; or treating hypertension) in all subtypes of acute stroke were included. The Cochrane Collaboration tool was used to assess the risk of bias. Data were analyzed using specific statistical methods.
RESULTS
Following the abstract and full-text screening, this meta-analysis included five retrospective cohorts and one prospective pseudorandomized cohort. Nicardipine's effect on time at goal BP was significantly superior to that of labetalol in patients with acute stroke (0.275 standardized mean difference [SMD], 95% confidence interval [CI]: 0.112-0.438, P = 0.001). The incidence of adverse events was significantly higher in the nicardipine group than that in the labetalol group. The pooled odds ratio (OR) was 1.509 (95% CI: 1.077-2.113, I = 0.00%, P = 0.757). The quality of included studies was found to be low.
CONCLUSION
More prospective, comparative trials are needed to investigate the efficacy of BP management as well as clinical outcomes in acute stroke patients receiving continuous labetalol and nicardipine infusions.
Topics: Humans; Labetalol; Nicardipine; Antihypertensive Agents; Retrospective Studies; Prospective Studies; Blood Pressure; Treatment Outcome; Hypertension; Stroke
PubMed: 36352567
DOI: 10.4103/0028-3886.359214 -
The Cochrane Database of Systematic... Feb 2015The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. Although shorter treatment courses may improve adherence, the WHO recommends at least three days of the short-acting artemisinin component to eliminate 90% P. falciparum parasites in the bloodstream, before leaving the longer-acting partner drug to clear the remaining parasites.
OBJECTIVES
To evaluate the efficacy and safety of the artemisinin-naphthoquine combination for treating adults and children with uncomplicated P. falciparum malaria.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; and LILACS up to January 2015. We also searched the metaRegister of Controlled Trials (mRCT) using 'malaria' and 'arte* OR dihydroarte*' as search terms.
SELECTION CRITERIA
Randomized controlled trials comparing artemisinin-naphthoquine combinations with established WHO-recommended ACTs for the treatment of adults and children with uncomplicated malaria due to P. falciparum.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy' and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
Four trials, enrolling 740 adults and children, met the inclusion criteria. Artemisinin-naphthoquine was administered as a single dose (two trials), as two doses given eight hours apart (one trial), and once daily for three days (one trial), and compared to three-day regimens of established ACTs. Three additional small pharmaceutical company trials have been carried out. We have requested the data but have not received a response from the company. Artemisinin-naphthoquine versus artemether-lumefantrineIn three small trials from Benin, Côte d'Ivoire, and Papua New Guinea, both combinations had a very low incidence of treatment failure at Day 28, and there were no differences demonstrated in PCR-unadjusted, or PCR-adjusted treatment failure (three trials, 487 participants, low quality evidence). Only the single study from Papua New Guinea followed participants up to Day 42, and the number of treatment failures remained very low with both combinations (one trial, 186 participants, very low quality evidence). Artemisinin-naphthoquine versus dihydroartemisinin-piperaquineIn a single small trial from Indonesia, treatment failure at Day 28 and Day 42 was very low in both groups with no differences demonstrated (one trial, 144 participants, very low quality evidence).
AUTHORS' CONCLUSIONS
The results of these few trials of artemisinin-naphthoquine are promising, but further trials from multiple settings are required to reliably demonstrate the relative efficacy and safety compared to established ACTs. Future trials should be adequately powered to demonstrate non-inferiority, and regimens incorporating three days of the artemisinin component are probably preferable to the one-day regimens.
Topics: Adult; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Drug Combinations; Ethanolamines; Fluorenes; Humans; Malaria, Falciparum; Naphthoquinones; Quinolines; Randomized Controlled Trials as Topic
PubMed: 25702785
DOI: 10.1002/14651858.CD011547 -
Journal of Human Hypertension Feb 2024Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating... (Meta-Analysis)
Meta-Analysis Review
Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.
Topics: Humans; Renin-Angiotensin System; Renin; Aldosterone; Blood Pressure; Norepinephrine; Epinephrine; Angiotensin II; Potassium; Sodium; Exercise
PubMed: 38017087
DOI: 10.1038/s41371-023-00872-4 -
The Cochrane Database of Systematic... Mar 2015Surgery on fingers is a common procedure in emergency and day care surgery. Adrenaline combined with lidocaine can prolong digital nerve block and provide a bloodless... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgery on fingers is a common procedure in emergency and day care surgery. Adrenaline combined with lidocaine can prolong digital nerve block and provide a bloodless operating field. Extended postoperative pain relief can reduce the need for analgesics and can facilitate hand rehabilitation. Conventionally, adrenaline is avoided at anatomical sites with end arteries such as digits, penis and pinna because of concerns about arterial spasm, ischaemia and gangrene distal to the site of drug infiltration.
OBJECTIVES
To assess the safety and efficacy of use of adrenaline (any dilution) combined with lidocaine (any dilution) for digital nerve blocks (fingers and toes).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2014), MEDLINE via Ovid SP (1966 to 18 November 2014) and EMBASE via Ovid SP (1980 to 18 November 2014). We also searched specific websites, such as www.indmed.nic.in; www.cochrane-sadcct.org; and www.Clinicaltrials.gov.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared the use of adrenaline with lidocaine and plain lidocaine in patients undergoing surgery on digits (fingers and toes). Our primary outcomes were duration of anaesthesia, adverse outcomes such as ischaemia distal to the injection site and cost analysis. Our secondary outcomes were duration of postoperative pain relief and reduced bleeding during surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. We performed all analyses on an intention-to-treat basis. We used a fixed-effect model when no evidence of significant heterogeneity between studies was found and a random-effects model when heterogeneity was likely.
MAIN RESULTS
We included four RCTs with 167 participants. Risk of bias of the included studies was high, as none of them reported method of randomization, allocation concealment or blinding. Only one trial mentioned our primary outcome of duration of anaesthesia. The mean difference in duration of anaesthesia with use of adrenaline with lidocaine was 3.20 hours (95% confidence interval (CI) 2.48 to 3.92 hours; one RCT, 20 participants; low-quality evidence). No trial reported adverse events such as ischaemia distal to the injection site, and no trial reported cost analysis. One trial mentioned the secondary outcome of duration of postoperative pain relief, but available data were insufficient for analysis of the findings. Two trials reported the secondary outcome of reduced bleeding during surgery.Bleeding during surgery was observed in nine out of 52 participants as compared with 25 out of 51 participants in the adrenaline with lidocaine and plain lidocaine groups, respectively. The risk ratio for bleeding in the adrenaline with lidocaine group was 0.35 (95% CI 0.19 to 0.65; two RCTs, 103 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
From the limited data available, evidence is insufficient to recommend use or avoidance of adrenaline in digital nerve blocks. The evidence provided in this review indicates that addition of adrenaline to lidocaine may prolong the duration of anaesthesia and reduce the risk of bleeding during surgery, although the quality of the evidence is low. We have identified the need for researchers to conduct large trials that focus on other important outcomes such as adverse events, cost analysis and duration of postoperative pain relief.
Topics: Adolescent; Adult; Anesthetics, Local; Child; Child, Preschool; Emergencies; Epinephrine; Female; Finger Injuries; Fingers; Humans; Infant; Lidocaine; Male; Nerve Block; Randomized Controlled Trials as Topic; Toes
PubMed: 25790261
DOI: 10.1002/14651858.CD010645.pub2 -
Advances in Nutrition (Bethesda, Md.) Dec 2022We studied associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children. We conducted a systematic review... (Meta-Analysis)
Meta-Analysis
We studied associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children. We conducted a systematic review followed by a meta-analysis and critical appraisal of human studies published from 1997 to 2021. Thirty publications were identified. The meta-analysis included 5 of 7 case-control studies studying neural tube defects (NTDs) in relation to maternal choline intakes/circulating concentrations. Low maternal choline intake/circulating concentrations were associated with a higher OR for NTDs among 1131 mothers of newborns with NTDs and 4439 control mothers (pooled estimate = 1.36; 95% CI: 1.11, 1.67). The 95% prediction intervals were 0.78, 2.36. Findings and critical evaluation of 10 publications with interventional designs showed that higher maternal choline intakes during the second half of pregnancy and early postnatal period (550 mg up to 1 g/d on top of the diet) or a child intake of 513 to 625 mg/d from supplements were safe and likely to demonstrate favorable effects on several domains of child neurocognition, such as memory, attention, and visuospatial learning versus the comparators. Findings from observational studies (n = 13) partly supported the association between maternal choline intake/serum concentrations and child neurocognition, but there was low confidence in the use of plasma choline concentrations as a choline intake marker. In conclusion, low maternal choline intakes were associated with a higher OR for NTDs. The risk could be up to 2.36-fold in some populations. Despite limitations of available trials and observational studies, higher maternal choline intake was likely to be associated with better child neurocognition/neurodevelopment. The results should be used to guide choline intake recommendations in pregnancy and lactation, especially because most young women are not achieving the reference intake of choline. This meta-analysis is registered at PROSPERO as CRD42021233790.
Topics: Pregnancy; Humans; Child; Infant, Newborn; Female; Choline; Dietary Supplements; Vitamins; Diet; Neural Tube Defects; Brain; Child Development
PubMed: 36041182
DOI: 10.1093/advances/nmac082 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs.
MAIN RESULTS
We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL. Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer.
AUTHORS' CONCLUSIONS
For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.
Topics: Fingolimod Hydrochloride; Glatiramer Acetate; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Rituximab; Young Adult
PubMed: 34748215
DOI: 10.1002/14651858.CD013874.pub2 -
The Cochrane Database of Systematic... Sep 2014Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
OBJECTIVES
To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
SEARCH METHODS
We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
DATA COLLECTION AND ANALYSIS
Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.
MAIN RESULTS
We included 12 trials of varying sample sizes (N = 9 to 135), mainly from high-income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) -4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD -0.2; 95% CI -4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).
AUTHORS' CONCLUSIONS
There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high-quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough.
Topics: Acetates; Adolescent; Adult; Albuterol; Anti-Inflammatory Agents; Bordetella pertussis; Child; Cough; Cyclopropanes; Dexamethasone; Diphenhydramine; Histamine H1 Antagonists; Humans; Immunoglobulins; Length of Stay; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Whooping Cough
PubMed: 25243777
DOI: 10.1002/14651858.CD003257.pub5 -
Chinese Medical Journal Sep 2017Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in... (Review)
Review
OBJECTIVE
Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest. The evidence for the use of adrenaline in out-of-hospital cardiac arrest (OHCA) and in-hospital resuscitation is inconclusive. We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients.
DATA SOURCES
The EMBASE and PubMed databases were searched with the key words "epinephrine," "cardiac arrest," and variations of these terms.
STUDY SELECTION
Data from clinical randomized trials, meta-analyses, guidelines, and recent reviews were selected for review.
RESULTS
Sudden cardiac arrest causes 544,000 deaths in China each year, with survival occurring in <1% of cases (compared with 12% in the United States). The American Heart Association recommends the use of epinephrine in patients with cardiac arrest, as part of advanced cardiac life support. There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation (ROSC). However, there are conflicting results regarding long-term survival and functional recovery, particularly neurological outcome, after CPR. There is currently insufficient evidence to support or reject epinephrine administration during resuscitation. We believe that epinephrine may have a role in resuscitation, as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses, which is an essential intermediate step toward long-term survival.
CONCLUSIONS
The administration of adrenaline was associated with improved short-term survival (ROSC). However, it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA, and it may have a harmful effect. Larger placebo-controlled, double-blind, randomized control trials are required to definitively establish the effect of epinephrine.
Topics: Cardiopulmonary Resuscitation; Epinephrine; Humans; Meta-Analysis as Topic; Out-of-Hospital Cardiac Arrest; Randomized Controlled Trials as Topic
PubMed: 28836556
DOI: 10.4103/0366-6999.213429