1. Home
  2. Randomized Controlled Trials as Topic

Randomized Controlled Trials as Topic

Drug Efficacy in the Treatment of Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-Analysis

Author/s: 
Gerolymos, C, Barazer, R, Yon, D.K., Loundou, A, Boyer, L, Fond, G

Importance: Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.

Objective: To compare the efficacy associated with AIA treatments.

Data sources: Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.

Study selection: Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.

Data extraction and synthesis: Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.

Main outcomes and measures: The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.

Results: Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.

Conclusions and relevance: In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.

Keywords 
Antipsychotic Agents akathisia biperiden trazodone cyproheptadine gallopamil propranolol vitamin B 6

Outpatient randomized controlled trials to reduce COVID-19 hospitalization: Systematic review and meta-analysis

Author/s: 
Daniele Focosi, David J. Sullivan, Daniel F. Hanley, Mario Cruciani, Massimo Franchini, Jiangda Ou, Arturo Casadevall, Nigel Paneth

This COVID-19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO-CRD42022369181). Risk of bias was extracted from COVID-19-NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID-19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24-0.40]) had highest hospital reduction efficacy, followed by COVID-19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53-0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48-1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72-0.93]). Earlier in disease onset interventions performed better than later. This meta-analysis allows approximate head-to-head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID-19 in the immunocompromised.

Keywords 
COVID-19 convalescent plasma monoclonal antibody outpatients randomized controlled trial small molecule antivirals

Is acupuncture an effective treatment for temporomandibular disorder?: A systematic review and meta-analysis of randomized controlled trials

Author/s: 
Park, Eun Young, Cho, Jae-Heung, Lee, Sook-Hyun, Kim, Koh-Woon, Ha, In-Hyuk, Lee, Yoon Jae

Background:
Acupuncture is used for treating various disorders, but its effects on temporomandibular disorder (TMD) remain unclear. This study aimed to assess the effectiveness and safety of acupuncture for TMD via a systematic review of randomized clinical trials.

Methods:
A total of 11 Korean and worldwide databases were searched to identify acupuncture studies in adults with TMD. A Cochrane risk of bias assessment was performed on all articles; a meta-analysis, which involved the categorization according to the type of control used (inactive control, active control, or add-on), was subsequently performed. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation methodology.

Results:
The qualitative analysis of randomized clinical trials with acupuncture as the intervention included 32 articles, 22 of which were included in the quantitative analysis (471 participants). Acupuncture significantly improved outcomes (effect rate, relative risk [RR]: 7.00, 95% confidence interval [CI]: 1.91, 25, 62; visual analog scale, standardized mean difference: 0.49, 95% CI: 0.24, 0.73) versus active controls (effect rate, RR: 1.19; 95% CI: 1.12, 1.27). In the analysis of add-ons, acupuncture significantly improved the effect rate and pain intensity (effect rate, RR: 1.36; 95% CI: 1.04, 1.77; visual analog scale, mean difference: −1.23; 95% CI −1.79, −0.67). However, the quality of evidence was determined to range from low to very low.

Conclusion:
Acupuncture in TMD significantly improved outcomes versus active controls and when add-on treatments were applied. However, as the quality of evidence was determined to be low, well-designed clinical trials should be conducted in the future.

Keywords 
Acupuncture

Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis

Author/s: 
Yin, X., Rodgers, A., Perkovic, A., Huang, L., Li, K., Yu, J., Wu, Y., Wu, J. H. Y., Marklund, M., Huffman, M. D., Miranda, J. J., Di Tanna, G. L., Labarthe, D., Elliott, P., Tian, M., Neal, B.

Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.

Methods We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.

Results There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).

Conclusions The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.

Keywords 
hypertension meta-analysis stroke Salt Substitutes blood pressure

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

Author/s: 
Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., Arya, R., Bainbridge, J., Bare, M., Bleck, T., Dodson, W. E., Garrity, L., Jagoda, A., Lowenstein, D., Pellock, J., Riviello, J., Sloan, E., Treiman, D. M.

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Author/s: 
McDonagh, M. S., Wagner, J., Ahmed, A. Y., Morasco, B., Kansagara, D., Chou, R.

Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain.

Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021.

Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects.

Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported.

Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

Malnutrition in hospitalized adults: A systematic review

Author/s: 
Uhl, S., Siddique, S. M., McKeever, L., Bloschichak, A., D'Anci, K., Leas, B., Mull, N. K, Tsou, A. Y.

Objectives. To review the association between malnutrition and clinical outcomes among hospitalized patients, evaluate effectiveness of measurement tools for malnutrition on clinical outcomes, and assess effectiveness of hospital-initiated interventions for patients diagnosed with malnutrition.

Data sources. We searched electronic databases (Embase®, MEDLINE®, PubMed®, and the Cochrane Library) from January 1, 2000, to June 3, 2021. We hand-searched reference lists of relevant studies and searched for unpublished studies in ClinicalTrials.gov.

Review methods. Using predefined criteria and dual review, we selected (1) existing systematic reviews (SRs) to assess the association between malnutrition and clinical outcomes, (2) randomized and non-randomized studies to evaluate the effectiveness of malnutrition tools on clinical outcomes, and (3) randomized controlled trials (RCTs) to assess effectiveness of hospital-initiated treatments for malnutrition. Clinical outcomes of interest included mortality, length of stay, 30-day readmission, quality of life, functional status, activities of daily living, hospital acquired conditions, wound healing, and discharge disposition. When appropriate, we conducted meta-analysis to quantitatively summarize study findings; otherwise, data were narratively synthesized. When available, we used pooled estimates from existing SRs to determine the association between malnutrition and clinical outcomes, and assessed the strength of evidence.

Results. Six existing SRs (including 43 unique studies) provided evidence on the association between malnutrition and clinical outcomes. Low to moderate strength of evidence (SOE) showed an association between malnutrition and increased hospital mortality and prolonged hospital length of stay. This association was observed across patients hospitalized for an acute medical event requiring intensive care unit care, heart failure, and cirrhosis. Literature searches found no studies that met inclusion criteria and assessed effectiveness of measurement tools. The primary reason studies did not meet inclusion criteria is because they lacked an appropriate control group. Moderate SOE from 11 RCTs found that hospital-initiated malnutrition interventions likely reduce mortality compared with usual care among hospitalized patients diagnosed with malnutrition. Low SOE indicated that hospital-initiated malnutrition interventions may also improve quality of life compared to usual care.

Conclusions. Evidence shows an association between malnutrition and increased mortality and prolonged length of hospital stay among hospitalized patients identified as malnourished. However, the strength of this association varied depending on patient population and tool used to identify malnutrition. Evidence indicates malnutrition-focused hospital-initiated interventions likely reduce mortality and may improve quality of life compared to usual care among patients diagnosed with malnutrition. Research is needed to assess the clinical utility of measurement tools for malnutrition.

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Author/s: 
Martineau, AR, Jolliffe, DA, Hooper, RL, Greenberg, L, Aloia, JF, Bergman, P, Dubnov-Raz, G, Esposito, S, Ganmaa, D, Ginde, AA, Goodall, EC, Grant, CC, Griffiths, CJ, Janssens, W, Laaksi, I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach, I, Kumar, GT, Urashima, M", CA Jr

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.

Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.

Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.

Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.

Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.

Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.

Systematic review registration PROSPERO CRD42014013953.

Keywords 
vitamin D respiratory tract infections dietary supplements

Exercise for dysmenorrhoea

Author/s: 
Armour, M, Ee, CC, Naidoo, D, Ayati, Z, Chalmers, KJ, Steel, KA, de Manincor, MJ, Delshad, E

BACKGROUND:

Exercise has a number of health benefits and has been recommended as a treatment for primary dysmenorrhoea (period pain), but the evidence for its effectiveness on primary dysmenorrhoea is unclear. This review examined the available evidence supporting the use of exercise to treat primary dysmenorrhoea.

OBJECTIVES:

To evaluate the effectiveness and safety of exercise for women with primary dysmenorrhoea.

SEARCH METHODS:

We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED and CINAHL (from inception to July 2019). We searched two clinical trial databases (inception to March 2019) and handsearched reference lists and previous systematic reviews.

SELECTION CRITERIA:

We included studies if they randomised women with moderate-to-severe primary dysmenorrhoea to receive exercise versus no treatment, attention control, non-steroidal anti-inflammatory drugs (NSAIDs) or the oral contraceptive pill. Cross-over studies and cluster-randomised trials were not eligible for inclusion.

DATA COLLECTION AND ANALYSIS:

Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. We contacted study authors for missing information. We assessed the quality of the evidence using GRADE. Our primary outcomes were menstrual pain intensity and adverse events. Secondary outcomes included overall menstrual symptoms, usage of rescue analgesic medication, restriction of daily life activities, absence from work or school and quality of life.

MAIN RESULTS:

We included a total of 12 trials with 854 women in the review, with 10 trials and 754 women in the meta-analysis. Nine of the 10 studies compared exercise with no treatment, and one study compared exercise with NSAIDs. No studies compared exercise with attention control or with the oral contraceptive pill. Studies used low-intensity exercise (stretching, core strengthening or yoga) or high-intensity exercise (Zumba or aerobic training); none of the included studies used resistance training.Exercise versus no treatmentExercise may have a large effect on reducing menstrual pain intensity compared to no exercise (standard mean difference (SMD) -1.86, 95% confidence interval (CI) -2.06 to -1.66; 9 randomised controlled trials (RCTs), n = 632; I2= 91%; low-quality evidence). This SMD corresponds to a 25 mm reduction on a 100 mm visual analogue scale (VAS) and is likely to be clinically significant. We are uncertain if there is any difference in adverse event rates between exercise and no treatment.We are uncertain if exercise reduces overall menstrual symptoms (as measured by the Moos Menstrual Distress Questionnaire (MMDQ)), such as back pain or fatigue compared to no treatment (mean difference (MD) -33.16, 95% CI -40.45 to -25.87; 1 RCT, n = 120; very low-quality evidence), or improves mental quality of life (MD 4.40, 95% CI 1.59 to 7.21; 1 RCT, n = 55; very low-quality evidence) or physical quality of life (as measured by the 12-Item Short Form Health Survey (SF-12)) compared to no exercise (MD 3.40, 95% CI -1.68 to 8.48; 1 RCT, n = 55; very low-quality evidence) when compared to no treatment. No studies reported on any changes in restriction of daily life activities or on absence from work or school.Exercise versus NSAIDsWe are uncertain if exercise, when compared with mefenamic acid, reduced menstrual pain intensity (MD -7.40, 95% CI -8.36 to -6.44; 1 RCT, n = 122; very low-quality evidence), use of rescue analgesic medication (risk ratio (RR) 1.77, 95% CI 1.21 to 2.60; 1 RCT, n = 122; very low-quality evidence) or absence from work or school (RR 1.00, 95% CI 0.49 to 2.03; 1 RCT, n = 122; very low-quality evidence). None of the included studies reported on adverse events, overall menstrual symptoms, restriction of daily life activities or quality of life.

AUTHORS' CONCLUSIONS:

The current low-quality evidence suggests that exercise, performed for about 45 to 60 minutes each time, three times per week or more, regardless of intensity, may provide a clinically significant reduction in menstrual pain intensity of around 25 mm on a 100 mm VAS. All studies used exercise regularly throughout the month, with some studies asking women not to exercise during menstruation. Given the overall health benefits of exercise, and the relatively low risk of side effects reported in the general population, women may consider using exercise, either alone or in conjunction with other modalities, such as NSAIDs, to manage menstrual pain. It is unclear if the benefits of exercise persist after regular exercise has stopped or if they are similar in women over the age of 25. Further research is required, using validated outcome measures, adequate blinding and suitable comparator groups reflecting current best practice or accounting for the extra attention given during exercise.

Keywords 
exercise menstruation menstrual pain dysmenorrhea cochrane review alternative therapies pelvic pain

Glucocorticoids for croup in children

Author/s: 
Gates, A, Gates, M, Vandermeer, B, Johnson, C, Hartling, L, Johnson, DW, Klassen, TP

BACKGROUND:

Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011.

OBJECTIVES:

To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years.

SEARCH METHODS:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies.

SELECTION CRITERIA:

We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events.

DATA COLLECTION AND ANALYSIS:

One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach.

MAIN RESULTS:

We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children.

AUTHORS' CONCLUSIONS:

Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Keywords 
croup children randomized control trial adolescent
Subscribe to Randomized Controlled Trials as Topic