-
BMJ (Clinical Research Ed.) Oct 2021To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip...
OBJECTIVE
To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES
The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS
Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS
192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS
Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO number CRD42020213656.
Topics: Acetaminophen; Administration, Oral; Administration, Topical; Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Network Meta-Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Management
PubMed: 34642179
DOI: 10.1136/bmj.n2321 -
BMJ (Clinical Research Ed.) Jul 2022To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis.
DESIGN
Systematic review and meta-analysis of randomised trials.
DATA SOURCES
Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment.
MAIN OUTCOME MEASURES
The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was -0.37 SMD. Serious adverse events were analysed as relative risks.
METHODS
Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed.
RESULTS
169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger's tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD -0.08, 95% confidence interval -0.15 to -0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect corresponds to a difference in pain scores of -2.0 mm (95% confidence interval -3.8 to -0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (relative risk 1.49, 95% confidence interval 1.12 to 1.98).
CONCLUSION
Strong conclusive evidence indicates that viscosupplementation leads to a small reduction in knee osteoarthritis pain compared with placebo, but the difference is less than the minimal clinically important between group difference. Strong conclusive evidence indicates that viscosupplementation is also associated with an increased risk of serious adverse events compared with placebo. The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021236894.
Topics: Humans; Viscosupplementation; Osteoarthritis, Knee; Pain Measurement; Pain
PubMed: 36333100
DOI: 10.1136/bmj-2022-069722 -
The Cochrane Database of Systematic... Feb 2023Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and improving asthma control. We therefore conducted an updated meta-analysis to include data from new trials completed since this date.
OBJECTIVES
To evaluate the effectiveness and safety of administration of vitamin D or its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control.
SEARCH METHODS
We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: 8 September 2022.
SELECTION CRITERIA
We included double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control, or both.
DATA COLLECTION AND ANALYSIS
Four review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). The primary outcome was the incidence of severe asthma exacerbations requiring treatment with systemic corticosteroids. Secondary outcomes included the incidence of asthma exacerbations precipitating an emergency department visit or requiring hospital admission, or both, end-study childhood Asthma Control Test (cACT) or Asthma Control Test (ACT) scores, and end-study % predicted forced expiratory volume in one second (FEV1). We performed subgroup analyses to determine whether the effect of vitamin D on risk of asthma exacerbation was modified by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, form of vitamin D given, and age of participants.
MAIN RESULTS
We included 20 studies in this review; 15 trials involving a total of 1155 children and five trials involving a total of 1070 adults contributed data to analyses. Participant ages ranged from 1 to 84 years, with two trials providing data specific to participants under five years (n = 69) and eight trials providing data specific to participants aged 5 to 16 (n = 766). Across the trials, 1245 participants were male and 1229 were female, with two studies not reporting sex distribution. Fifteen trials contributed to the primary outcome analysis of exacerbations requiring systemic corticosteroids. The duration of trials ranged from three to 40 months; all but two investigated effects of administering cholecalciferol (vitamin D3). As in the previous Cochrane Review, the majority of participants had mild to moderate asthma, and profound vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25 nmol/L) at baseline was rare. Administration of vitamin D or its hydroxylated metabolites did not reduce or increase the proportion of participants experiencing one or more asthma exacerbations treated with systemic corticosteroids (odds ratio (OR) 1.04, 95% CI 0.81 to 1.34; I = 0%; 14 studies, 1778 participants; high-quality evidence). This equates to an absolute risk of 226 per 1000 (95% CI 185 to 273) in the pooled vitamin D group, compared to a baseline risk of 219 participants per 1000 in the pooled placebo group. We also found no effect of vitamin D supplementation on the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.86, 95% CI 0.62 to 1.19; I = 60%; 10 studies, 1599 participants; high-quality evidence), or the time to first exacerbation (hazard ratio 0.82, 95% CI 0.59 to 1.15; I = 22%; 3 studies, 850 participants; high-quality evidence). Subgroup analysis did not reveal any evidence of effect modification by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, or age. A single trial investigating administration of calcidiol reported a benefit of the intervention for the primary outcome of asthma control. Vitamin D supplementation did not influence any secondary efficacy outcome meta-analysed, which were all based on moderate- or high-quality evidence. We observed no effect on the incidence of serious adverse events (OR 0.89, 95% CI 0.56 to 1.41; I = 0%; 12 studies, 1556 participants; high-quality evidence). The effect of vitamin D on fatal asthma exacerbations was not estimable, as no such events occurred in any trial. Six studies reported adverse reactions potentially attributable to vitamin D. These occurred across treatment and control arms and included hypercalciuria, hypervitaminosis D, kidney stones, gastrointestinal symptoms and mild itch. In one trial, we could not ascertain the total number of participants with hypercalciuria from the trial report. We assessed three trials as being at high risk of bias in at least one domain; none of these contributed data to the analysis of the outcomes reported above. Sensitivity analyses that excluded these trials from each outcome to which they contributed did not change the null findings.
AUTHORS' CONCLUSIONS
In contrast to findings of our previous Cochrane Review on this topic, this updated review does not find evidence to support a role for vitamin D supplementation or its hydroxylated metabolites to reduce risk of asthma exacerbations or improve asthma control. Participants with severe asthma and those with baseline 25(OH)D concentrations < 25 nmol/L were poorly represented, so further research is warranted here. A single study investigating effects of calcidiol yielded positive results, so further studies investigating effects of this metabolite are needed.
Topics: Adult; Child; Humans; Male; Female; Infant; Child, Preschool; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Calcifediol; Hypercalciuria; Disease Progression; Asthma; Vitamins; Adrenal Cortex Hormones; Vitamin D; Cholecalciferol; Anti-Asthmatic Agents; Randomized Controlled Trials as Topic
PubMed: 36744416
DOI: 10.1002/14651858.CD011511.pub3 -
BMJ (Clinical Research Ed.) Feb 2020To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration.
DESIGN
Systematic review and meta-analysis following PRISMA guidelines.
DATA SOURCES
Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019.
INCLUSION CRITERIA
Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion.
DATA EXTRACTION AND ANALYSIS
Two of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression.
RESULTS
133 studies with 12 197 participants were included. The mean reductions (reduced sodium usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days' duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction.
CONCLUSIONS
The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019140812.
Topics: Blood Pressure; Blood Pressure Determination; Diet, Sodium-Restricted; Dose-Response Relationship, Drug; Humans; Hypertension; Randomized Controlled Trials as Topic; Sodium Chloride, Dietary
PubMed: 32094151
DOI: 10.1136/bmj.m315 -
The Cochrane Database of Systematic... Mar 2021Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many...
BACKGROUND
Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits.
OBJECTIVES
To assess the effects of interventions for cutaneous disease in SLE.
SEARCH METHODS
We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence.
MAIN RESULTS
Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate.
AUTHORS' CONCLUSIONS
Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.
Topics: Age of Onset; Azathioprine; Bias; Biological Factors; Chloroquine; Cosmetic Techniques; Cyclosporine; Dermatologic Agents; Exanthema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Medicine, Chinese Traditional; Methotrexate; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Skin Diseases; Symptom Flare Up
PubMed: 33687069
DOI: 10.1002/14651858.CD007478.pub2 -
The Cochrane Database of Systematic... Dec 2020The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to increasing rates of neonatal abstinence syndrome (NAS). Neonatal opioid withdrawal syndrome (NOWS) is a newer term describing the subset of NAS related to opioid exposure. Non-pharmacological care is the first-line treatment for substance withdrawal in newborns. Despite the widespread use of non-pharmacological care to mitigate symptoms of NAS, there is not an established definition of, and standard for, non-pharmacological care practices in this population. Evaluation of safety and efficacy of non-pharmacological practices could provide clear guidance for clinical practice.
OBJECTIVES
To evaluate the safety and efficacy of non-pharmacological treatment of infants at risk for, or having symptoms consistent with, opioid withdrawal on the length of hospitalization and use of pharmacological treatment for symptom management. Comparison 1: in infants at risk for, or having early symptoms consistent with, opioid withdrawal, does non-pharmacological treatment reduce the length of hospitalization and use of pharmacological treatment? Comparison 2: in infants receiving pharmacological treatment for symptoms consistent with opioid withdrawal, does concurrent non-pharmacological treatment reduce duration of pharmacological treatment, maximum and cumulative doses of opioid medication, and length of hospitalization?
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 10); Ovid MEDLINE; and CINAHL on 11 October 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster trials.
SELECTION CRITERIA
We included trials comparing single or bundled non-pharmacological interventions to no non-pharmacological treatment or different single or bundled non-pharmacological interventions. We assessed non-pharmacological interventions independently and in combination based on sufficient similarity in population, intervention, and comparison groups studied. We categorized non-pharmacological interventions as: modifying environmental stimulation, feeding practices, and support of the mother-infant dyad. We presented non-randomized studies identified in the search process narratively.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Primary outcomes in infants at risk for, or having early symptoms consistent with, opioid withdrawal included length of hospitalization and pharmacological treatment with one or more doses of opioid or sedative medication. Primary outcomes in infants receiving opioid treatment for symptoms consistent with opioid withdrawal included length of hospitalization, length of pharmacological treatment with opioid or sedative medication, and maximum and cumulative doses of opioid medication.
MAIN RESULTS
We identified six RCTs (353 infants) in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated between 1975 and 2018. We identified no RCTs in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. The certainty of evidence for all outcomes was very low to low. We also identified and excluded 34 non-randomized studies published between 2005 and 2018, including 29 in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated and five in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. We identified seven preregistered interventional clinical trials that may qualify for inclusion at review update when complete. Of the six RCTs, four studies assessed modifying environmental stimulation in the form of a mechanical rocking bed, prone positioning, non-oscillating waterbed, or a low-stimulation nursery; one study assessed feeding practices (comparing 24 kcal/oz to 20 kcal/oz formula); and one study assessed support of the maternal-infant dyad (tailored breastfeeding support). There was no evidence of a difference in length of hospitalization in the one study that assessed modifying environmental stimulation (mean difference [MD) -1 day, 95% confidence interval [CI) -2.82 to 0.82; 30 infants; very low-certainty evidence) and the one study of support of the maternal-infant dyad (MD -8.9 days, 95% CI -19.84 to 2.04; 14 infants; very low-certainty evidence). No studies of feeding practices evaluated the length of hospitalization. There was no evidence of a difference in use of pharmacological treatment in three studies of modifying environmental stimulation (typical risk ratio [RR) 1.00, 95% CI 0.86 to 1.16; 92 infants; low-certainty evidence), one study of feeding practices (RR 0.92, 95% CI 0.63 to 1.33; 49 infants; very low-certainty evidence), and one study of support of the maternal-infant dyad (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). Reported secondary outcomes included neonatal intensive care unit (NICU) admission, days to regain birth weight, and weight nadir. One study of support of the maternal-infant dyad reported NICU admission (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). One study of feeding practices reported days to regain birth weight (MD 1.10 days, 95% CI 2.76 to 0.56; 46 infants; very low-certainty evidence). One study that assessed modifying environmental stimulation reported weight nadir (MD -0.28, 95% CI -1.15 to 0.59; 194 infants; very low-certainty evidence) and one study of feeding practices reported weight nadir (MD -0.8, 95% CI -2.24 to 0.64; 46 infants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether non-pharmacological care for opioid withdrawal in newborns affects important clinical outcomes including length of hospitalization and use of pharmacological treatment based on the six included studies. The outcomes identified for this review were of very low- to low-certainty evidence. Combined analysis was limited by heterogeneity in study design and intervention definitions as well as the number of studies. Many prespecified outcomes were not reported. Although caregivers are encouraged by experts to optimize non-pharmacological care for opioid withdrawal in newborns prior to initiating pharmacological care, we do not have sufficient evidence to inform specific clinical practices. Larger well-designed studies are needed to determine the effect of non-pharmacological care for opioid withdrawal in newborns.
Topics: Beds; Breast Feeding; Environment Design; Humans; Hypnotics and Sedatives; Infant Equipment; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Narcotics; Neonatal Abstinence Syndrome; Nurseries, Infant; Opiate Substitution Treatment; Patient Positioning; Prone Position; Randomized Controlled Trials as Topic
PubMed: 33348423
DOI: 10.1002/14651858.CD013217.pub2 -
The Cochrane Database of Systematic... Mar 2020Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL) therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD.
OBJECTIVES
To evaluate the effectiveness and safety of intense pulsed light (IPL) for the management dry eye disease resulting from meibomian gland dysfunction (MGD).
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase Ovid and three trial registers for eligible clinical trials on 1 August 2019. There were no restrictions on publication status, date or language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) studying the effectiveness or safety of IPL for treating MGD.
DATA COLLECTION AND ANALYSIS
Our outcomes of interest were the change from baseline in subjective dry eye symptoms, adverse events, changes to lipid layer thickness, tear break-up time (TBUT), tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland dropout, corneal sodium fluorescein staining and conjunctival lissamine green staining. Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE Working Group approach.
MAIN RESULTS
We included three RCTs, one from New Zealand, one from Japan and one from China, published between 2015 and 2019. Together, these trials enrolled 114 adults (228 eyes). Two studies used a paired-eye (inter-eye comparison) design to evaluate the effects of a sham (control) IPL treatment relative to an actual IPL treatment. One study randomised individuals to either an IPL intervention combined with meibomian gland expression (MGX), or MGX alone (standard therapy). The study follow-up periods ranged from 45 days to nine months. None of the trials were at low risk of bias in all seven domains. The first authors of two included studies were in receipt of funding from patents or the manufacturers of IPL devices. The funding sources and declaration of interests were not given in the report of the third included trial. All three trials evaluated the effect of IPL on dry eye symptoms, quantified using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Pooling data from two trials that used a paired-eye design, the summary estimate for these studies indicated little to no reduction in dry eye symptoms with IPL relative to a sham intervention (mean difference (MD) -0.33 units, 95% confidence interval (CI) -2.56 to 1.89; I² = 0%; 2 studies, 144 eyes). The other study was not pooled as it had a unit-of-analysis error, but reported a reduction in symptoms in favour of IPL (MD -4.60, 95% CI -6.72 to -2.48; 84 eyes). The body of evidence for this outcome was of very low certainty, so we are uncertain about the effect of IPL on dry eye symptoms. There were no relevant combinable data for any of the other secondary outcomes, thus the effect of IPL on clinical parameters relevant to dry eye disease are currently unclear. For sodium fluorescein TBUT, two studies indicated that there may be an improvement in favour of IPL (MD 2.02 seconds, 95% CI 0.87 to 3.17; MD 2.40 seconds, 95% CI 2.27 to 2.53; 172 eyes total; low-certainty evidence). We are uncertain of the effect of IPL on non-invasive tear break-up time (MD 5.51 seconds, 95% CI 0.79 to 10.23; MD 3.20, 95% CI 3.09 to 3.31 seconds; two studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, one study indicated that there may be an improvement in favour of IPL (MD -7.00 mOsmol/L, 95% -12.97 to -1.03; 56 eyes; low-certainty evidence). We are uncertain of the effect of IPL on meibomian gland orifice plugging (MD -1.20 clinical units, 95% CI -1.24 to -1.16; 84 eyes; very low-certainty evidence). We are uncertain of the effect of IPL on corneal sodium fluorescein staining. One study reported no evidence of a difference between the IPL and sham intervention arms at three months of follow-up (P = 0.409), and a second study reported data favouring IPL (MD -1.00 units, 95% CI -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). We considered the incidence of adverse events at the study endpoint, as a measure of safety. As most trials did not specifically report adverse events, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggest some adverse effects that may be experienced by participants, include mild pain and burning, and the potential for partially losing eyelashes (due to clinician error).
AUTHORS' CONCLUSIONS
This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.
Topics: Dry Eye Syndromes; Humans; Intense Pulsed Light Therapy; Meibomian Gland Dysfunction; Randomized Controlled Trials as Topic
PubMed: 32182637
DOI: 10.1002/14651858.CD013559 -
The Cochrane Database of Systematic... Feb 2023The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective...
BACKGROUND
The copper intrauterine device (Cu-IUD) is a highly effective method of contraception that can also be used for emergency contraception (EC). It is the most effective form of EC, and is more effective than other existing oral regimens also used for EC. The Cu-IUD provides the unique benefit of providing ongoing contraception after it is inserted for EC; however, uptake of this intervention has been limited. Progestin IUDs are a popular method of long-acting, reversible contraception. If these devices were also found to be effective for EC, they would provide a critical additional option for women. These IUDs could not only provide EC and ongoing contraception, but additional non-contraceptive benefits, including a reduction in menstrual bleeding, cancer prevention, and pain management.
OBJECTIVES
To examine the safety and effectiveness of progestin-containing IUDs for emergency contraception, compared with copper-containing IUDs, or compared with dedicated oral hormonal methods.
SEARCH METHODS
We considered all randomized controlled trials and non-randomized studies of interventions that compared outcomes for individuals seeking a levonorgestrel IUD (LNG-IUD) for EC to a Cu-IUD or dedicated oral EC method. We considered full-text studies, conference abstracts, and unpublished data. We considered studies irrespective of their publication status and language of publication.
SELECTION CRITERIA
We included studies comparing progestin IUDs with copper-containing IUDs, or oral EC methods for emergency contraception.
DATA COLLECTION AND ANALYSIS
We systematically searched nine medical databases, two trials registries, and one gray literature site. We downloaded all titles and abstracts retrieved by electronic searching to a reference management database, and removed duplicates. Three review authors independently screened titles, abstracts, and full-text reports to determine studies eligible for inclusion. We followed standard Cochrane methodology to assess risk of bias, and analyze and interpret the data. We used GRADE methodology to assess the certainty of the evidence.
MAIN RESULTS
We included only one relevant study (711 women); a randomized, controlled, non-inferiority trial comparing LNG-IUDs to Cu-IUDs for EC, with a one-month follow-up. With one study, the evidence was very uncertain for the difference in pregnancy rates, failed insertion rates, expulsion rates, removal rates and the difference in the acceptability of the IUDs. There was also uncertain evidence suggesting the Cu-IUD may slightly increase rates of cramping and the LNG-IUD may slightly increase bleeding and spotting days. AUTHORS' CONCLUSIONS: This review is limited in its ability to provide definitive evidence regarding the LNG-IUD's equivalence, superiority, or inferiority to the Cu-IUD for EC. Only one study was identified in the review, which had possible risks of bias related to randomization and rare outcomes. Additional studies are needed to provide definitive evidence related to the effectiveness of the LNG-IUD for EC.
Topics: Female; Humans; Pregnancy; Contraception, Postcoital; Copper; Intrauterine Devices; Intrauterine Devices, Copper; Progestins; Randomized Controlled Trials as Topic; Steroids
PubMed: 36847591
DOI: 10.1002/14651858.CD013744.pub2 -
The Cochrane Database of Systematic... May 2022Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (250 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants) but not tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. Across comparison groups, the same study found no evidence of a difference in vision changes and inconsistent evidence with regard to quality of life. Evidence on quality of life as assessed by the physical (MD 8.17, 95% CI 4.44 to 11.90) and mental (MD 5.61, 95% CI 0.06 to 11.16) component score of the 36-Item Short Form Health Survey (SF-36) favored weekly tocilizumab versus placebo + 52-week taper but not bi-weekly tocillizumab versus placebo + 26-week taper (moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Female; Giant Cell Arteritis; Humans; Male; Recurrence
PubMed: 35560150
DOI: 10.1002/14651858.CD013484.pub3 -
The Cochrane Database of Systematic... Aug 2021Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (251 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. The same study found no evidence of a difference between groups with regard to vision changes and quality of life, except for the assessment of quality of life with the physical component score of the 36-Item Short Form Health Survey (SF-36), which favored weekly tocilizumab versus placebo + 52-week taper (MD 8.17, 95% CI 4.44 to 11.90; moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Aged; Antibodies, Monoclonal, Humanized; Canada; Female; Giant Cell Arteritis; Humans; Male
PubMed: 34420204
DOI: 10.1002/14651858.CD013484.pub2