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Gastroenterology Feb 2022Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis
Efficacy of Biologic Drugs in Short-Duration Versus Long-Duration Inflammatory Bowel Disease: A Systematic Review and an Individual-Patient Data Meta-Analysis of Randomized Controlled Trials.
BACKGROUND AND AIMS
Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD).
METHODS
This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome.
RESULTS
We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09-1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01-2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19-1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti-tumor necrosis factor exposure.
CONCLUSIONS
There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Certolizumab Pegol; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Agents; Humans; Immunologic Factors; Infliximab; Natalizumab; Randomized Controlled Trials as Topic; Tumor Necrosis Factor Inhibitors
PubMed: 34757139
DOI: 10.1053/j.gastro.2021.10.037 -
Systematic Reviews Oct 2023Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different...
BACKGROUND AND OBJECTIVE
Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment.
METHODS
The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference.
RESULTS
Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943-2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM).
DISCUSSION
The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020.
Topics: Humans; Bias; Homeopathy; Research Design; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37805577
DOI: 10.1186/s13643-023-02313-2 -
The Cochrane Database of Systematic... Feb 2022Transient tachypnoea of the newborn (TTN) is characterised by tachypnoea and signs of respiratory distress. It is caused by delayed clearance of lung fluid at birth. TTN... (Review)
Review
BACKGROUND
Transient tachypnoea of the newborn (TTN) is characterised by tachypnoea and signs of respiratory distress. It is caused by delayed clearance of lung fluid at birth. TTN typically appears within the first two hours of life in term and late preterm newborns. Although it is usually a self-limited condition, admission to a neonatal unit is frequently required for monitoring, the provision of respiratory support, and drugs administration. These interventions might reduce respiratory distress during TTN and enhance the clearance of lung liquid. The goals are reducing the effort required to breathe, improving respiratory distress, and potentially shortening the duration of tachypnoea. However, these interventions might be associated with harm in the infant.
OBJECTIVES
The aim of this overview was to evaluate the benefits and harms of different interventions used in the management of TTN.
METHODS
We searched the Cochrane Database of Systematic Reviews on 14 July 2021 for ongoing and published Cochrane Reviews on the management of TTN in term (> 37 weeks' gestation) or late preterm (34 to 36 weeks' gestation) infants. We included all published Cochrane Reviews assessing the following categories of interventions administered within the first 48 hours of life: beta-agonists (e.g. salbutamol and epinephrine), corticosteroids, diuretics, fluid restriction, and non-invasive respiratory support. The reviews compared the above-mentioned interventions to placebo, no treatment, or other interventions for the management of TTN. The primary outcomes of this overview were duration of tachypnoea and the need for mechanical ventilation. Two overview authors independently checked the eligibility of the reviews retrieved by the search and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We used the GRADE approach to assess the certainty of evidence for effects of interventions for TTN management. As all of the included reviews reported summary of findings tables, we extracted the information already available and re-graded the certainty of evidence of the two primary outcomes to ensure a homogeneous assessment. We provided a narrative summary of the methods and results of each of the included reviews and summarised this information using tables and figures.
MAIN RESULTS
We included six Cochrane Reviews, corresponding to 1134 infants enrolled in 18 trials, on the management of TTN in term and late preterm infants, assessing salbutamol (seven trials), epinephrine (one trial), budesonide (one trial), diuretics (two trials), fluid restriction (four trials), and non-invasive respiratory support (three trials). The quality of the included reviews was high, with all of them fulfilling the critical domains of the AMSTAR 2. The certainty of the evidence was very low for the primary outcomes, due to the imprecision of the estimates (few, small included studies) and unclear or high risk of bias. Salbutamol may reduce the duration of tachypnoea compared to placebo (mean difference (MD) -16.83 hours, 95% confidence interval (CI) -22.42 to -11.23, 2 studies, 120 infants, low certainty evidence). We did not identify any review that compared epinephrine or corticosteroids to placebo and reported on the duration of tachypnoea. However, one review reported on "trend of normalisation of respiratory rate", a similar outcome, and found no differences between epinephrine and placebo (effect size not reported). The evidence is very uncertain regarding the effect of diuretics compared to placebo (MD -1.28 hours, 95% CI -13.0 to 10.45, 2 studies, 100 infants, very low certainty evidence). We did not identify any review that compared fluid restriction to standard fluid rates and reported on the duration of tachypnoea. The evidence is very uncertain regarding the effect of continuous positive airway pressure (CPAP) compared to free-flow oxygen therapy (MD -21.1 hours, 95% CI -22.9 to -19.3, 1 study, 64 infants, very low certainty evidence); the effect of nasal high-frequency (oscillation) ventilation (NHFV) compared to CPAP (MD -4.53 hours, 95% CI -5.64 to -3.42, 1 study, 40 infants, very low certainty evidence); and the effect of nasal intermittent positive pressure ventilation (NIPPV) compared to CPAP on duration of tachypnoea (MD 4.30 hours, 95% CI -19.14 to 27.74, 1 study, 40 infants, very low certainty evidence). Regarding the need for mechanical ventilation, the evidence is very uncertain for the effect of salbutamol compared to placebo (risk ratio (RR) 0.60, 95% CI 0.13 to 2.86, risk difference (RD) 10 fewer, 95% CI 50 fewer to 30 more per 1000, 3 studies, 254 infants, very low certainty evidence); the effect of epinephrine compared to placebo (RR 0.67, 95% CI 0.08 to 5.88, RD 70 fewer, 95% CI 460 fewer to 320 more per 1000, 1 study, 20 infants, very low certainty evidence); and the effect of corticosteroids compared to placebo (RR 0.52, 95% CI 0.05 to 5.38, RD 40 fewer, 95% CI 170 fewer to 90 more per 1000, 1 study, 49 infants, very low certainty evidence). We did not identify a review that compared diuretics to placebo and reported on the need for mechanical ventilation. The evidence is very uncertain regarding the effect of fluid restriction compared to standard fluid administration (RR 0.73, 95% CI 0.24 to 2.23, RD 20 fewer, 95% CI 70 fewer to 40 more per 1000, 3 studies, 242 infants, very low certainty evidence); the effect of CPAP compared to free-flow oxygen (RR 0.30, 95% CI 0.01 to 6.99, RD 30 fewer, 95% CI 120 fewer to 50 more per 1000, 1 study, 64 infants, very low certainty evidence); the effect of NIPPV compared to CPAP (RR 4.00, 95% CI 0.49 to 32.72, RD 150 more, 95% CI 50 fewer to 350 more per 1000, 1 study, 40 infants, very low certainty evidence); and the effect of NHFV versus CPAP (effect not estimable, 1 study, 40 infants, very low certainty evidence). Regarding our secondary outcomes, duration of hospital stay was the only outcome reported in all of the included reviews. One trial on fluid restriction reported a lower duration of hospitalisation in the restricted-fluids group, but with very low certainty of evidence. The evidence was very uncertain for the effects on secondary outcomes for the other five reviews. Data on potential harms were scarce, as all of the trials were underpowered to detect possible increases in adverse events such as pneumothorax, arrhythmias, and electrolyte imbalances. No adverse effects were reported for salbutamol; however, this medication is known to carry a risk of tachycardia, tremor, and hypokalaemia in other settings.
AUTHORS' CONCLUSIONS
This overview summarises the evidence from six Cochrane Reviews of randomised trials regarding the effects of postnatal interventions in the management of TTN. Salbutamol may reduce the duration of tachypnoea slightly. We are uncertain as to whether salbutamol reduces the need for mechanical ventilation. We are uncertain whether epinephrine, corticosteroids, diuretics, fluid restriction, or non-invasive respiratory support reduces the duration of tachypnoea and the need for mechanical ventilation, due to the extremely limited evidence available. Data on harms were lacking.
Topics: Humans; Infant; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Oxygen Inhalation Therapy; Systematic Reviews as Topic; Transient Tachypnea of the Newborn
PubMed: 35199848
DOI: 10.1002/14651858.CD013563.pub2 -
The Cochrane Database of Systematic... Jan 2021Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day-to-day activities and overall quality of life. In carefully selected patients with COPD, long-term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations.
OBJECTIVES
To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta-analyses (NMAs), and to provide rankings of identified antibiotics.
SEARCH METHODS
To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020.
SELECTION CRITERIA
We included RCTs with a parallel design of at least 12 weeks' duration evaluating long-term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD.
DATA COLLECTION AND ANALYSIS
This Cochrane Review collected and updated pair-wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta-analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study's contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events.
MAIN RESULTS
Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single-centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV₁) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect-fixed class effect: mean difference (MD) -2.30, 95% CrI -3.61 to -0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect-fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance.
AUTHORS' CONCLUSIONS
This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade-off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non-tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non-tuberculous mycobacteria.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Load; Bayes Theorem; Bias; Disease Progression; Female; Forced Expiratory Volume; Humans; Macrolides; Male; Middle Aged; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Randomized Controlled Trials as Topic; Tetracyclines; Treatment Outcome
PubMed: 33448349
DOI: 10.1002/14651858.CD013198.pub2 -
Cardiovascular and Interventional... Jan 2021Objective To systematically review the published literature on genicular artery embolization (GAE) for osteoarthritis (OA) related knee pain. Materials and Methods Using... (Meta-Analysis)
Meta-Analysis
Objective To systematically review the published literature on genicular artery embolization (GAE) for osteoarthritis (OA) related knee pain. Materials and Methods Using three databases, a systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcome measures included the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results Three single-arm studies were included from an initial search yielding 305 results. One hundred and eighty-six knees in 133 patients with either mild-to-moderate (174/186, 94%) or severe (12/186, 6%) OA underwent embolization with either imipenem/cilastatin sodium (159/186, 85%) or embozene (27/186, 15%). Technical success was 100%. Average VAS improved from baseline at 1 day, 1 week, 1 month, 3 months, 4 months, 6 months, 1 year and 2 years (66.5 at baseline vs 33.5, 32.7, 33.8, 28.9, 29.0, 22.3, 14.8 and 14.0, respectively). Average WOMAC scores improved from baseline at 1, 3, 4, 6, 12 and 24 months (45.7 at baseline vs 24.0, 31.0, 14.8, 14.6, 8.2 and 6.2). Severe OA in 12 cases showed initially improved VAS, but was not sustained. Minor adverse events such as erythema in the region of embolization (21/186, 11%), puncture-site hematoma (18/186, 10%), paresthesia (2/186, 1%) and fever (1/186, 0.5%) were reported. Conclusion Limited single-arm studies report GAE is promising for treating OA-related pain. Most treatments performed for mild-to-moderate OA demonstrated durable clinical responses from 6 months to 4 years. Limited data for severe OA suggest a non-durable response. Future studies should be standardized to facilitate comparison and control for placebo effect.
Topics: Arthralgia; Embolization, Therapeutic; Humans; Leg; Osteoarthritis, Knee; Pain Management; Pain Measurement; Treatment Outcome
PubMed: 33135117
DOI: 10.1007/s00270-020-02687-z -
Clinical Orthopaedics and Related... Feb 2020To improve ankle stability in patients who have experienced an ankle sprain with residual symptoms of instability and/or objective joint laxity, external supports (such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To improve ankle stability in patients who have experienced an ankle sprain with residual symptoms of instability and/or objective joint laxity, external supports (such as taping, bracing, and orthotic insoles) are used sometimes. However, available randomized trials have disagreed on whether restraints improve balance in those individuals. In this situation, a network meta-analysis can help because it allows for comparing multiple treatments simultaneously, taking advantage not only of direct but also indirect evidence synthesis.
QUESTIONS/PURPOSES
The aim of this network meta-analysis was to assess (1) the impact of taping and orthotic devices on dynamic postural control in individuals with ankle instability and (2) the presence of a placebo effect in participants treated with sham taping and complications resulting from the administered treatments.
METHODS
We searched the PubMed, Scopus, and CENTRAL databases up to February 13, 2019 for completed studies. Randomized trials assessing the results of real and/or sham taping, wait-and-see protocols, ankle bracing, and foot orthotics for ankle instability as determined by one or more ankle sprains followed by ongoing subjective symptoms and/or mechanical laxity were included. We evaluated dynamic postural control in terms of the Star Excursion Balance Test in the posteromedial direction (SEBT-PM), which is considered the most representative of balance deficits in patients with ankle instability. Standardized mean differences were re-expressed to percentage differences in SEBT-PM, with higher scores representing possible improvement. Subsequently, those data were checked against the established minimal detectable change of 14% for this scale to make judgements on clinical importance. We also assessed the presence of a placebo effect by comparing the results of sham taping with no treatment and complications resulting from the administered treatments. Additionally, we judged the quality of trials using the Cochrane risk of bias tool and quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. A total of 22 trials met our inclusion criteria, 18 of which were deemed to be at a low risk of bias. A network of treatments consisting of 13 studies was created, and the level of evidence was judged to be high. As far as participants' allocation to treatment arms, 85 patients followed a wait-and-see protocol, 29 received placebo taping, 99 were treated with taping, 16 were treated with bracing, 27 were administered insoles, and six individuals were offered a combination of insoles with bracing. Of note, with statistical power set at 80%, a minimum of 16 patients per treatment group was required to provide sufficient statistical power and detect a SEBT-PM percentage difference of 14%.
RESULTS
A network meta-analysis did not demonstrate a benefit of taping or bracing over no treatment (percentage difference in SEBT-PM between taping and bracing versus control: -2.4 [95% CI -6 to 1.1]; p = 0.18, and -7.5 [95% CI -15.9 to 1]; p = 0.08, respectively). This was also the case for sham taping because the measurement increase failed to exceed the minimal detectable change (percentage difference in SEBT-PM between sham taping and untreated control: -1.1 [95% CI -6.9 to 4.7]; p = 0.72). Importantly, there were no reported adverse events after treatment application.
CONCLUSIONS
Evidence of moderate strength indicated that external supports of any type were no more effective than controls in improving dynamic postural control in patients with at least one ankle sprain and residual functional or mechanical deficits. Therefore, implementing those tools as a standalone treatment does not appear to be a viable strategy for the primary management of ankle instability. It is conceivable that combinations of rehabilitation and external supports could be more effective than external supports alone, and future trials should evaluate the potential of such combinations in enhancing not only clinician-reported but also patient-oriented outcomes using long-term follow-up measurements.
LEVEL OF EVIDENCE
Level I, therapeutic study.
Topics: Ankle Injuries; Ankle Joint; Athletic Tape; Biomechanical Phenomena; Chronic Disease; Equipment Design; Humans; Joint Instability; Network Meta-Analysis; Orthopedic Procedures; Orthotic Devices; Postural Balance; Randomized Controlled Trials as Topic; Range of Motion, Articular; Recovery of Function; Treatment Outcome
PubMed: 31625960
DOI: 10.1097/CORR.0000000000000946 -
Annals of Behavioral Medicine : a... Oct 2022Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect.
PURPOSE
To estimate the effect size of choice on the placebo effect and identify any moderators of this effect.
METHODS
Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice.
RESULTS
Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges' g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice.
CONCLUSIONS
Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.
Topics: Anxiety Disorders; Humans; Placebo Effect; Reproducibility of Results; Research Design; Sleep Initiation and Maintenance Disorders
PubMed: 35022650
DOI: 10.1093/abm/kaab111 -
Clinical Orthopaedics and Related... Apr 2022Tennis elbow is a common painful enthesopathy of the lateral elbow that limits upper limb function and frequently results in lost time at work. Surgeons often recommend... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tennis elbow is a common painful enthesopathy of the lateral elbow that limits upper limb function and frequently results in lost time at work. Surgeons often recommend surgery if symptoms persist despite nonsurgical management, but operations for tennis elbow are inconsistent in their efficacy, and what we know about those operations often derives from observational studies that assume the condition does not continue to improve over time. This assumption is largely untested, and it may not be true; meta-analyzing results from the control arms of tennis elbow studies can help us to evaluate this premise, but to our knowledge, this has not been done.
QUESTIONS/PURPOSES
The aims of this systematic review were to describe the course of (1) global improvement, (2) pain, and (3) disability in participants who received no active treatment (placebo or no treatment) in published randomized controlled trials (RCTs) on tennis elbow. We also assessed (4) whether the duration of symptoms or placebo effect is associated with differences in symptom trajectories.
METHODS
We searched MEDLINE, Embase, and CENTRAL from database inception to August 12, 2019, for trials including participants with tennis elbow and a placebo or a no-treatment arm and a minimum follow-up duration of 6 months. There were no language restrictions or exclusion criteria. We extracted global improvement, pain, and disability outcomes. We used the Cochrane Risk of Bias tool to assess the risk of bias of included trials. To estimate the typical course of tennis elbow without active treatment, we pooled global improvement (the proportion of participants who reported feeling much better or completely recovered), mean pain, and mean disability using baseline, 1-month, 3-month, 6-month, and 12-month follow-up data. We transformed pain and disability data from the original papers so that at each timepoint the relevant outcome was expressed as change relative to baseline to account for different baseline values. We used meta-regression to assess whether the placebo effect or duration of symptoms before enrollment was associated with differences in symptom trajectories. We included 24 trials with 1085 participants who received no active treatment.
RESULTS
The number of patients who were not improved decreased exponentially over time. The half-life of global improvement was between 2.5 and 3 months (that is, every 2.5 to 3 months, 50% of the remaining symptomatic patients reported complete recovery or greatly improved symptoms). At 1 year, 89% (189 of 213; 95% CI 80% to 97%) of patients experienced global improvement. The mean pain and disability followed a similar pattern, halving every 3 to 4 months. Eighty-eight percent of pain (95% CI 70% to 100%) and 85% of disability (95% CI 60% to 100%) had resolved by 1 year. The mean duration of symptoms before trial enrollment was not associated with differences in symptom trajectories. The trajectories of the no-treatment and placebo arms were similar, indicating that the placebo effect of the studied active treatments likely is negligible.
CONCLUSION
Based on the placebo or no-treatment control arms of randomized trials, about 90% of people with untreated tennis elbow achieve symptom resolution at 1 year. The probability of resolution appears to remain constant throughout the first year of follow-up and does not depend on previous symptom duration, undermining the rationale that surgery is appropriate if symptoms persist beyond a certain point of time. We recommend that clinicians inform people who are frustrated with persisting symptoms that this is not a cause for apprehension, given that spontaneous improvement is about as likely during the subsequent few months as it was early after the symptoms first appeared. Because of the high likelihood of spontaneous recovery, any active intervention needs to be justified by high levels of early efficacy and little or no risk to outperform watchful waiting.
LEVEL OF EVIDENCE
Level I, therapeutic study.
Topics: Elbow; Humans; Pain; Prognosis; Tennis Elbow
PubMed: 34874323
DOI: 10.1097/CORR.0000000000002058 -
The Cochrane Database of Systematic... Oct 2018Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome. This Cochrane Review is an updated review, first published in 2001 and subsequently updated in 2007 and 2014.
OBJECTIVES
To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 September 2017), and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined as systolic blood pressure 140 to 169 mmHg and/or diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
For this update, we included 63 trials (data from 58 trials, 5909 women), with moderate to high risk of bias overall.We carried out GRADE assessments for the main 'antihypertensive drug versus placebo/no antihypertensive drug' comparison only. Evidence was graded from very low to moderate certainty, with downgrading mainly due to design limitations and imprecision.For many outcomes, trials contributing data evaluated different hypertensive drugs; while we did not downgrade for this indirectness, results should be interpreted with caution.Antihypertensive drug versus placebo/no antihypertensive drug (31 trials, 3485 women)Primary outcomes: moderate-certainty evidence suggests that use of antihypertensive drug(s) probably halves the risk of developing severe hypertension (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; 20 trials, 2558 women), but may have little or no effect on the risk of proteinuria/pre-eclampsia (average risk ratio (aRR) 0.92; 95% CI 0.75 to 1.14; 23 trials, 2851 women; low-certainty evidence). Moderate-certainty evidence also shows that antihypertensive drug(s) probably have little or no effect in the risk of total reported fetal or neonatal death (including miscarriage) (aRR 0.72; 95% CI 0.50 to 1.04; 29 trials, 3365 women), small-for-gestational-age babies (aRR 0.96; 95% CI 0.78 to 1.18; 21 trials, 2686 babies) or preterm birth less than 37 weeks (aRR 0.96; 95% CI 0.83 to 1.12; 15 trials, 2141 women).
SECONDARY OUTCOMES
we are uncertain of the effect of antihypertensive drug(s) on the risk of maternal death, severe pre-eclampsia, or eclampsia, orimpaired long-term growth and development of the baby in infancy and childhood, because the certainty of this evidence is very low. There may be little or no effect on the risk of changed/stopped drugs due to maternal side-effects, or admission to neonatal or intensive care nursery (low-certainty evidence). There is probably little or no difference in the risk of elective delivery (moderate-certainty evidence).Antihypertensive drug versus another antihypertensive drug (29 trials, 2774 women)Primary outcomes: beta blockers and calcium channel blockers together in the meta-analysis appear to be more effective than methyldopa in avoiding an episode of severe hypertension (RR 0.70; 95% CI 0.56 to 0.88; 11 trials, 638 women). There was also an increase in this risk when other antihypertensive drugs were compared with calcium channel blockers (RR 1.86; 95% CI 1.09 to 3.15; 5 trials, 223 women), but no evidence of a difference when methyldopa and calcium channel blockers together were compared with beta blockers (RR1.18, 95% CI 0.95 to 1.48; 10 trials, 692 women). No evidence of a difference in the risk of proteinuria/pre-eclampsia was found when alternative drugs were compared with methyldopa (aRR 0.78; 95% CI 0.58 to 1.06; 11 trials, 997 women), with calcium channel blockers (aRR: 1.24, 95% CI 0.70 to 2.19; 5 trials, 375 women), or with beta blockers (aRR 1.21, 95% CI 0.88 to 1.67; 12 trials, 1107 women).For the babies, we found no evidence of a difference in the risk oftotal reported fetal or neonatal death (including miscarriage) when comparing other antihypertensive drugs with methyldopa (aRR 0.77, 95% CI 0.52 to 1.14; 22 trials, 1791 babies), with calcium channel blockers (aRR 0.90, 95% CI 0.52 to 1.57; nine trials, 700 babies), or with beta blockers (aRR: 1.23, 95% CI 0.81 to 1.88; 19 trials, 1652 babies); nor in the risk for small-for-gestational age in the comparison with methyldopa (aRR 0.79, 95% CI 0.52 to 1.20; seven trials, 597 babies), with calcium channel blockers (aRR 1.05, 95% CI 0.64 to 1.73; four trials, 200 babies), or with beta blockers (average RR 1.13, 95% CI 0.80 to 1.60; 7 trials, 680 babies). No evidence of an overall difference among groups in the risk of preterm birth (less than 37 weeks) was found in the comparison with methyldopa (aRR: 0.91; 95% CI 0.68 to 1.22; 11 trials, 835 women), with calcium channel blockers (aRR 0.85, 95% CI 0.59 to 1.23; six trials, 330 women), or with beta blockers (aRR 1.22, 95% CI 0.90 to 1.66; 9 trials, 806 women).
SECONDARY OUTCOMES
There were no cases of maternal death andeclampsia. There is no evidence of a difference in the risk of severe pre-eclampsia, changed/stopped drug due to maternal side-effects, elective delivery, admission to neonatal or intensive care nursery when other antihypertensive drugs are compared with methyldopa, calcium channel blockers or beta blockers. Impaired long-term growth and development in infancy and childhood was not reported for these comparisons.
AUTHORS' CONCLUSIONS
Antihypertensive drug therapy for mild to moderate hypertension during pregnancy reduces the risk of severe hypertension. The effect on other clinically important outcomes remains unclear. If antihypertensive drugs are used, beta blockers and calcium channel blockers appear to be more effective than the alternatives for preventing severe hypertension. High-quality large sample-sized randomised controlled trials are required in order to provide reliable estimates of the benefits and adverse effects of antihypertensive treatment for mild to moderate hypertension for both mother and baby, as well as costs to the health services, women and their families.
Topics: Antihypertensive Agents; Female; Fetal Death; Humans; Hypertension; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Maternal Death; Placebo Effect; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Randomized Controlled Trials as Topic
PubMed: 30277556
DOI: 10.1002/14651858.CD002252.pub4 -
The Journal of International Medical... Jun 2020To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea.
METHODS
Relevant studies were searched in multiple databases. The weighted mean difference (WMD) was used as the effect indicator for measurement data, and each effect size was given estimates and 95% confidence intervals (CIs).
RESULTS
Nine studies with 647 patients were selected. Compared with the results in the control group, pain intensity was significantly relieved in the trial group when assessed by the intervention (cinnamon placebo: WMD = 1.815, 95% CI = 1.330-2.301; fennel placebo: WMD = 0.528, 95% CI = 0.119-6.829; ginger placebo: WMD = 2.902, 95% CI = 2.039-3.765), observation period (one cycle: WMD = 2.061, 95% CI = 0.815-3.307; one cycles: WMD = 1.831, 95% CI = 0.973-2.690), and study quality (high quality: WMD = 2.224, 95% CI = 1.488-2.960). Pain duration was significantly shorter in the trial group (cinnamon placebo: WMD = 16.200, 95% CI = 15.271-17.129). No publication bias was observed for either outcome.
CONCLUSIONS
For primary dysmenorrhea, cinnamon/fennel/ginger effectively reduced pain intensity, and cinnamon shortened the duration of pain. Further studies are needed to confirm our results.
Topics: Cinnamomum zeylanicum; Dysmenorrhea; Female; Foeniculum; Zingiber officinale; Herbal Medicine; Humans; Randomized Controlled Trials as Topic
PubMed: 32603204
DOI: 10.1177/0300060520936179