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Systematic Reviews Oct 2022This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral...
BACKGROUND
This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs.
METHODS
We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews.
RESULTS
We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients' choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin.
CONCLUSIONS
For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017084263-one deviation; efficacy and safety were from one review.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Genotype; Stroke; Venous Thromboembolism; Warfarin; Review Literature as Topic
PubMed: 36303235
DOI: 10.1186/s13643-022-02098-w -
Clinical Nutrition (Edinburgh, Scotland) Apr 2016There is limited information about the economic impact of nutritional support despite its known clinical benefits. This systematic review examined the cost and cost... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
There is limited information about the economic impact of nutritional support despite its known clinical benefits. This systematic review examined the cost and cost effectiveness of using standard (non-disease specific) oral nutritional supplements (ONS) administered in the hospital setting only.
METHODS
A systematic literature search of multiple databases, data synthesis and analysis were undertaken according to recommended procedures.
RESULTS
Nine publications comprising four full text papers, two abstracts and three reports, one of which contained 11 cost analyses of controlled cohort studies, were identified. Most of these were based on retrospective analyses of randomised controlled trials designed to assess clinically relevant outcomes. The sample sizes of patients with surgical, orthopaedic and medical problems and combinations of these varied from 40 to 1.16 million. Of 14 cost analyses comparing ONS with no ONS (or routine care), 12 favoured the ONS group, and among those with quantitative data (12 studies) the mean cost saving was 12.2%. In a meta-analysis of five abdominal surgical studies in the UK, the mean net cost saving was £746 per patient (se £338; P = 0.027). Cost savings were typically associated with significantly improved outcomes, demonstrated through the following meta-analyses: reduced mortality (Risk ratio 0.650, P < 0.05; N = 5 studies), reduced complications (by 35% of the total; P < 0.001, N = 7 studies) and reduced length of hospital stay (by ∼2 days, P < 0.05; N = 5 surgical studies) corresponding to ∼13.0% reduction in hospital stay. Two studies also found ONS to be cost effective, one by avoiding development of pressure ulcers and releasing hospital beds, and the other by gaining quality adjusted life years.
CONCLUSION
This review suggests that standard ONS in the hospital setting produce a cost saving and are cost effective. The evidence base could be further strengthened by prospective studies in which the primary outcome measures are economic.
Topics: Administration, Oral; Cost-Benefit Analysis; Dietary Supplements; Hospitals; Humans; Micronutrients; Models, Economic; Observational Studies as Topic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 26123475
DOI: 10.1016/j.clnu.2015.05.010 -
International Braz J Urol : Official... 2016Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The... (Review)
Review
Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics - pillars of the overactive bladder pharmacotherapy - started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning - as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder - 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.
Topics: Administration, Oral; Adrenergic beta-3 Receptor Agonists; Botulinum Toxins; Female; Humans; Male; Muscarinic Antagonists; Time Factors; Transcutaneous Electric Nerve Stimulation; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 27176185
DOI: 10.1590/S1677-5538.IBJU.2015.0367 -
The Cochrane Database of Systematic... Apr 2016Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports that suggest that oral immunoglobulins (Ig)A and IgG produce an immunoprotective effect in the gastrointestinal mucosa.
OBJECTIVES
To determine the effect of oral immunoglobulin on the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016), CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference proceedings.
SELECTION CRITERIA
All randomized or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against NEC in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or both, neonates.
DATA COLLECTION AND ANALYSIS
We performed data collection and analysis in accordance with the standard methods of the Cochrane Neonatal Review Group.
MAIN RESULTS
The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants).
AUTHORS' CONCLUSIONS
Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.
Topics: Administration, Oral; Enterocolitis, Necrotizing; Humans; Immunoglobulin A; Immunoglobulin G; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Randomized Controlled Trials as Topic
PubMed: 27040323
DOI: 10.1002/14651858.CD001816.pub3 -
The Cochrane Database of Systematic... Apr 2018Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen.
OBJECTIVES
To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy.
SEARCH METHODS
We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017).
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy.
DATA COLLECTION AND ANALYSIS
We retrieved 97 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We rated the quality of evidence for all outcomes using GRADE.
MAIN RESULTS
We included 10 RCTs that met our inclusion criteria, that involved a total of 439 children (oral immunotherapy 249; control intervention 190), aged 1 year to 18 years. Each study used a different oral immunotherapy protocol; none used sublingual immunotherapy. Three studies used placebo and seven used an egg avoidance diet as the control. Primary outcomes were: an increased amount of egg that can be ingested and tolerated without adverse events while receiving allergen-specific oral immunotherapy or sublingual immunotherapy, compared to control; and a complete recovery from egg allergy after completion of oral immunotherapy or sublingual immunotherapy, compared to control. Most children (82%) in the oral immunotherapy group could ingest a partial serving of egg (1 g to 7.5 g) compared to 10% of control group children (RR 7.48, 95% CI 4.91 to 11.38; RD 0.73, 95% CI 0.67 to 0.80). Fewer than half (45%) of children receiving oral immunotherapy were able to tolerate a full serving of egg compared to 10% of the control group (RR 4.25, 95% CI 2.77 to 6.53; RD 0.35, 95% CI 0.28 to 0.43). All 10 trials reported numbers of children with serious adverse events (SAEs) and numbers of children with mild-to-severe adverse events. SAEs requiring epinephrine/adrenaline presented in 21/249 (8.4%) of children in the oral immunotherapy group, and none in the control group. Mild-to-severe adverse events were frequent; 75% of children presented mild-to-severe adverse events during oral immunotherapy treatment versus 6.8% of the control group (RR 8.35, 95% CI 5.31 to 13.12). Of note, seven studies used an egg avoidance diet as the control. Adverse events occurred in 4.2% of children, which may relate to accidental ingestion of egg-containing food. Three studies used a placebo control with adverse events present in 2.6% of children. Overall, there was inconsistent methodological rigour in the trials. All studies enrolled small numbers of children and used different methods to provide oral immunotherapy. Eight included studies were judged to be at high risk of bias in at least one domain. Furthermore, the quality of evidence was judged to be low due to small numbers of participants and events, and possible biases.
AUTHORS' CONCLUSIONS
Frequent and increasing exposure to egg over one to two years in people who are allergic to egg builds tolerance, with almost everyone becoming more tolerant compared with a minority in the control group and almost half of people being totally tolerant of egg by the end of treatment compared with 1 in 10 people who avoid egg. However, nearly all who received treatment experienced adverse events, mainly allergy-related. We found that 1 in 12 children had serious allergic reactions requiring adrenaline, and some people gave up oral immunotherapy. It appears that oral immunotherapy for egg allergy is effective, but confidence in the trade-off between benefits and harms is low; because there was a small number of trials with few participants, and methodological problems with some trials.
Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Desensitization, Immunologic; Egg Hypersensitivity; Egg Proteins, Dietary; Epinephrine; Humans; Immunoglobulin E; Infant; Randomized Controlled Trials as Topic; Sublingual Immunotherapy
PubMed: 29676439
DOI: 10.1002/14651858.CD010638.pub3 -
The Cochrane Database of Systematic... Apr 2015Multiple sclerosis (MS) often leads to severe neurological disability and a serious decline in quality of life. The ideal target of disease-modifying therapy for MS is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) often leads to severe neurological disability and a serious decline in quality of life. The ideal target of disease-modifying therapy for MS is to prevent disability worsening and improve quality of life. Dimethyl fumarate is considered to have an immunomodulatory activity and neuroprotective effect. It has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency as a first-line therapy for adult patients with relapsing-remitting MS (RMSS).
OBJECTIVES
To assess the benefit and safety of dimethyl fumarate as monotherapy or combination therapy versus placebo or other approved disease-modifying drugs (interferon beta, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, alemtuzumab) for patients with MS.
SEARCH METHODS
The Trials Search Co-ordinator searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (4 June 2014). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to June 2014) from the MS societies in Europe and America. We also communicated with investigators participating in trials of dimethyl fumarate and the Biogen Idec Medical Information.
SELECTION CRITERIA
We included randomised, controlled, parallel-group clinical trials (RCTs) with a length of follow-up equal to or greater than one year evaluating dimethyl fumarate, as monotherapy or combination therapy, versus placebo or other approved disease-modifying drugs for patients with MS without restrictions regarding dosage, administration frequency and duration of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures of The Cochrane Collaboration. 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
Two RCTs were included, involving 2667 adult patients with RRMS to evaluate the efficacy and safety of two dosages of dimethyl fumarate (240 mg orally three times daily or twice daily) by direct comparison with placebo for two years. Among them, a subsample of 1221 (45.8%) patients were selected to participate in MRI evaluations by each study site with MRI capabilities itself. No powered head-to-head study with an active treatment comparator has been found. Meta-analyses showed that dimethyl fumarate both three times daily and twice daily reduced the number of patients with a relapse (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.50 to 0.66, P < 0.00001 and 0.64, 95% CI 0.54 to 0.77, P < 0.00001, respectively) or disability worsening (RR 0.70, 95% CI 0.57 to 0.87, P = 0.0009 and 0.65, 95% CI 0.53 to 0.81, P = 0.0001, respectively) over two years, compared to placebo. The treatment effects were decreased in the likely-case scenario analyses taking the effect of dropouts into consideration. Both dosages also reduced the annualised relapse rate. Data of active lesions on MRI scans were not combined because there was a high risk of selection bias for MRI outcomes and imprecision of MRI data in both studies, as well as an obvious heterogeneity between the studies. In terms of safety profile, both dosages increased the risk for adverse events and the risk for drug discontinuation due to adverse events. The most common adverse events included flushing and gastrointestinal events (upper abdominal pain, nausea and diarrhoea). Uncommon adverse events included lymphopenia and leukopenia, but they were more likely to happen with dimethyl fumarate than with placebo (high dosage: RR 5.25, 95% CI 2.20 to 12.51, P = 0.0002 and 5.23, 95% CI 2.47 to 11.07, P < 0.0001, respectively; low dosage: RR 5.69, 95% CI 2.40 to 13.46, P < 0.0001 and 6.53, 95% CI 3.13 to 13.64, P < 0.00001, respectively). Both studies had a high attrition bias resulting from the unbalanced reasons for dropouts among groups. Quality of evidence for relapse outcome was moderate, but for disability worsening was low.
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to support that dimethyl fumarate at a dose of 240 mg orally three times daily or twice daily reduces both the number of patients with a relapse and the annualised relapse rate over two years of treatment in comparison with placebo. However, the quality of the evidence to support the benefit in reducing the number of patients with disability worsening is low. There is no high-quality data available to evaluate the benefit on MRI outcomes. The common adverse effects such as flushing and gastrointestinal events are mild-to-moderate for most patients. Lymphopenia and leukopenia are uncommon adverse events but significantly associated with dimethyl fumarate. Both dosages of dimethyl fumarate have similar benefit and safety profile, which supports the option of low-dose administration. New studies of high quality and long-term follow-up are needed to evaluate the benefit of dimethyl fumarate on prevention of disability worsening and to observe the long-term adverse effects including progressive multifocal leukoencephalopathy.
Topics: Administration, Oral; Adult; Dimethyl Fumarate; Drug Administration Schedule; Fumarates; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 25900414
DOI: 10.1002/14651858.CD011076.pub2 -
The Journal of Clinical Pediatric... Sep 2023Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This... (Meta-Analysis)
Meta-Analysis
Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This systematic review and meta-analysis aimed to evaluate the association between JIA and periodontal diseases to facilitate oral health management and periodontal disease prevention in JIA patients. We conducted a comprehensive search of Web of Science, Cochrane Library, PubMed, Embase, Chinese Scientific and Technological Journal (VIP) database, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) up to 30 September 2022, without publication dates or language restrictions. Two authors independently evaluated observational studies for inclusion, and the quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). Continuous variables are presented as mean difference (MD) and 95% confidence interval (CI). Parameters of the simplified oral hygiene index (OHI-S), plaque index (PI), gingival index (GI), clinical attachment loss (CAL), and probing depth (PD) were considered as outcome measures and were compared between JIA patients and healthy controls. The initial search comprised 15 studies with a total of 1537 individuals. The meta-analysis showed the parameters of OHI-S (MD = 0.12, 95% CI: 0.04-0.19, = 0.002), PI (MD = 2.08, 95% CI: 1.67-2.50, < 0.00001), GI (MD = 0.50, 95% CI: 0.17-0.82, = 0.003), CAL (MD = 0.22, 95% CI: 0.01-0.43, = 0.04), and PD (MD = 1.42, 95% CI: 0.08-2.77, = 0.04) in JIA patients were significantly higher than those of healthy controls. All of the included studies were of high quality. This systematic review and meta-analysis showed a possible association between JIA and periodontal diseases. Therefore, it is recommended to continuously pay attention to the periodontal health of JIA patients and fully explore the underlying mechanism.
Topics: United States; Humans; Arthritis, Juvenile; Periodontal Diseases; Administration, Oral; Databases, Factual; Oral Health
PubMed: 37732432
DOI: 10.22514/jocpd.2023.050 -
The Cochrane Database of Systematic... May 2017Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review.
OBJECTIVES
To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials.
MAIN RESULTS
We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were concerns surrounding allocation concealment. There were no significant differences between people receiving supplements or dietary advice alone for change in weight, height, body mass index, z score or other indices of nutrition or growth. Changes in weight (kg) at three, six and 12 months respectively were: mean difference (MD) 0.32 (95% confidence interval (CI) -0.09 to 0.72); MD 0.47 (95% CI -0.07 to 1.02 ); and MD 0.16 (-0.68 to 1.00). Total calorie intake was greater in people taking supplements at 12 months, MD 265.70 (95% CI 42.94 to 488.46). There were no significant differences between the groups for anthropometric measures of body composition, lung function, gastro-intestinal adverse effects or activity levels. Moderate quality evidence exists for the outcomes of changes in weight and height and low quality evidence exists for the outcomes of change in total calories, total fat and total protein intake as results are applicable only to children between the ages of 2 and 15 years and many post-treatment diet diaries were not returned. Evidence for the rate of adverse events in the treatment groups was extremely limited and judged to be of very low quality AUTHORS' CONCLUSIONS: Oral calorie supplements do not confer any additional benefit in the nutritional management of moderately malnourished children with cystic fibrosis over and above the use of dietary advice and monitoring alone. While nutritional supplements may be used, they should not be regarded as essential. Further randomised controlled trials are needed to establish the role of short-term oral protein energy supplements in people with cystic fibrosis and acute weight loss and also for the long-term nutritional management of adults with cystic fibrosis or advanced lung disease, or both.
Topics: Administration, Oral; Adult; Child; Child Nutrition Disorders; Cystic Fibrosis; Dietary Supplements; Energy Intake; Humans; Randomized Controlled Trials as Topic
PubMed: 28470972
DOI: 10.1002/14651858.CD000406.pub5 -
The Cochrane Database of Systematic... May 2016Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular.
OBJECTIVES
To determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions.
SELECTION CRITERIA
Randomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics.
DATA COLLECTION AND ANALYSIS
Two authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison.
MAIN RESULTS
We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants)There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants)One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants)Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants)Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants)Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence).
AUTHORS' CONCLUSIONS
We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures.
Topics: Administration, Intranasal; Administration, Oral; Adult; Anxiety; Child; Chloral Hydrate; Diagnostic Techniques and Procedures; Diazepam; Humans; Hypnotics and Sedatives; Injections, Intravenous; Midazolam; Randomized Controlled Trials as Topic; Therapeutics
PubMed: 27198122
DOI: 10.1002/14651858.CD009491.pub2 -
Archives of Gynecology and Obstetrics Sep 2023Misoprostol is a synthetic PGE analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Misoprostol is a synthetic PGE analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit maternal and neonatal adverse outcomes. The present meta-analysis investigates the efficacy and safety of oral compared to vaginally inserted misoprostol in terms of induction of labor and adverse peripartum outcomes.
METHODS
We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till April 2022. Randomized controlled trials that assessed the efficacy of oral misoprostol (per os or sublingual) compared to vaginally inserted misoprostol. Effect sizes were calculated in R. Sensitivity analysis was performed to evaluate the possibility of small study effects, p-hacking. Meta-regression and subgroup analysis according to the dose of misoprostol was also investigated. The methodological quality of the included studies was assessed by two independent reviewers using the risk of bias 2 tool. Quality of evidence for primary outcomes was evaluated under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, ranging from very low to high.
RESULTS
Overall, 57 studies were included that involved 10,975 parturient. Their risk of bias ranged between low-moderate. There were no differences among the routes of intake in terms of successful vaginal delivery within 24 h (RR 0.90, 95% CI 0.80) and cesarean section rates (RR 0.92, 95% CI 0.82, 1.04). Sublingual misoprostol was superior compared to vaginal misoprostol in reducing the interval from induction to delivery (MD - 1.11 h, 95% CI - 2.06, - 0.17). On the other hand, per os misoprostol was inferior compared to vaginal misoprostol in terms of this outcome (MD 3.45 h, 95% CI 1.85, 5.06). Maternal and neonatal morbidity was not affected by the route or dose of misoprostol.
CONCLUSION
The findings of our study suggest that oral misoprostol intake is equally safe to vaginal misoprostol in terms of inducing labor at term. Sublingual intake seems to outperform the per os and vaginal routes without increasing the accompanying morbidity. Increasing the dose of misoprostol does not seem to increase its efficacy.
CLINICAL TRIAL REGISTRATION
Open Science Framework ( https://doi.org/10.17605/OSF.IO/V9JHF ).
Topics: Infant, Newborn; Pregnancy; Humans; Female; Misoprostol; Oxytocics; Cesarean Section; Labor, Induced; Administration, Sublingual
PubMed: 36472645
DOI: 10.1007/s00404-022-06867-9