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The Cochrane Database of Systematic... Jul 2019Work-related musculoskeletal disorders are a group of musculoskeletal disorders that comprise one of the most common disorders related to occupational sick leave...
BACKGROUND
Work-related musculoskeletal disorders are a group of musculoskeletal disorders that comprise one of the most common disorders related to occupational sick leave worldwide. Musculoskeletal disorders accounted for 21% to 28% of work absenteeism days in 2017/2018 in the Netherlands, Germany and the UK. There are several interventions that may be effective in tackling the high prevalence of work-related musculoskeletal disorders among workers, such as physical, cognitive and organisational interventions. In this review, we will focus on work breaks as a measure of primary prevention, which are a type of organisational intervention.
OBJECTIVES
To compare the effectiveness of different work-break schedules for preventing work-related musculoskeletal symptoms and disorders in healthy workers, when compared to conventional or alternate work-break schedules.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, SCOPUS, Web of Science, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform, to April/May 2019. In addition, we searched references of the included studies and of relevant literature reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of work-break interventions for preventing work-related musculoskeletal symptoms and disorders among workers. The studies were eligible for inclusion when intervening on work-break frequency, duration and/or type, compared to conventional or an alternate work-break intervention. We included only those studies in which the investigated population included healthy, adult workers, who were free of musculoskeletal complaints during study enrolment, without restrictions to sex or occupation. The primary outcomes were newly diagnosed musculoskeletal disorders, self-reported musculoskeletal pain, discomfort or fatigue, and productivity or work performance. We considered workload changes as secondary outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts and full texts for study eligibility, extracted data and assessed risk of bias. We contacted authors for additional study data where required. We performed meta-analyses, where possible, and we assessed the overall quality of the evidence for each outcome of each comparison using the five GRADE considerations.
MAIN RESULTS
We included six studies (373 workers), four parallel RCTs, one cross-over RCT, and one combined parallel plus cross-over RCT. At least 295 of the employees were female and at least 39 male; for the remaining 39 employees, the sex was not specified in the study trial. The studies investigated different work-break frequencies (five studies) and different work-break types (two studies). None of the studies investigated different work-break durations. We judged all studies to have a high risk of bias. The quality of the evidence for the primary outcomes of self-reported musculoskeletal pain, discomfort and fatigue was low; the quality of the evidence for the primary outcomes of productivity and work performance was very low. The studies were executed in Europe or Northern America, with none from low- to middle-income countries. One study could not be included in the data analyses, because no detailed results have been reported.Changes in the frequency of work breaksThere is low-quality evidence that additional work breaks may not have a considerable effect on musculoskeletal pain, discomfort or fatigue, when compared with no additional work breaks (standardised mean difference (SMD) -0.08; 95% CI -0.35 to 0.18; three studies; 225 participants). Additional breaks may not have a positive effect on productivity or work performance, when compared with no additional work breaks (SMD -0.07; 95% CI -0.33 to 0.19; three studies; 225 participants; very low-quality evidence).We found low-quality evidence that additional work breaks may not have a considerable effect on participant-reported musculoskeletal pain, discomfort or fatigue (MD 1.80 on a 100-mm VAS scale; 95% CI -41.07 to 64.37; one study; 15 participants), when compared to work breaks as needed (i.e. microbreaks taken at own discretion). There is very low-quality evidence that additional work breaks may have a positive effect on productivity or work performance, when compared to work breaks as needed (MD 542.5 number of words typed per 3-hour recording session; 95% CI 177.22 to 907.78; one study; 15 participants).Additional higher frequency work breaks may not have a considerable effect on participant-reported musculoskeletal pain, discomfort or fatigue (MD 11.65 on a 100-mm VAS scale; 95% CI -41.07 to 64.37; one study; 10 participants; low-quality evidence), when compared to additional lower frequency work breaks. We found very low-quality evidence that additional higher frequency work breaks may not have a considerable effect on productivity or work performance (MD -83.00 number of words typed per 3-hour recording session; 95% CI -305.27 to 139.27; one study; 10 participants), when compared to additional lower frequency work breaks.Changes in the duration of work breaksNo trials were identified that assessed the effect of different durations of work breaks.Changes in the type of work breakWe found low-quality evidence that active breaks may not have a considerable positive effect on participant-reported musculoskeletal pain, discomfort and fatigue (MD -0.17 on a 1-7 NRS scale; 95% CI -0.71 to 0.37; one study; 153 participants), when compared to passive work breaks.Relaxation work breaks may not have a considerable effect on participant-reported musculoskeletal pain, discomfort or fatigue, when compared to physical work breaks (MD 0.20 on a 1-7 NRS scale; 95% CI -0.43 to 0.82; one study; 97 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
We found low-quality evidence that different work-break frequencies may have no effect on participant-reported musculoskeletal pain, discomfort and fatigue. For productivity and work performance, evidence was of very low-quality that different work-break frequencies may have a positive effect. For different types of break, there may be no effect on participant-reported musculoskeletal pain, discomfort and fatigue according to low-quality evidence. Further high-quality studies are needed to determine the effectiveness of frequency, duration and type of work-break interventions among workers, if possible, with much higher sample sizes than the studies included in the current review. Furthermore, work-break interventions should be reconsidered, taking into account worker populations other than office workers, and taking into account the possibility of combining work-break intervention with other interventions such as ergonomic training or counselling, which may may possibly have an effect on musculoskeletal outcomes and work performance.
Topics: Adult; Ergonomics; Health Personnel; Health Workforce; Humans; Musculoskeletal Diseases; Occupational Diseases; Personnel Staffing and Scheduling; Randomized Controlled Trials as Topic; Workplace
PubMed: 31334564
DOI: 10.1002/14651858.CD012886.pub2 -
The Journal of Pain 2020Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment.
OBJECTIVE
To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia.
METHODS
The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals.
RESULTS
Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made.
CONCLUSIONS
tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies.
PERSPECTIVE
This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.
Topics: Chronic Pain; Clinical Trials as Topic; Fibromyalgia; Humans; Pain Management; Transcranial Direct Current Stimulation; Treatment Outcome
PubMed: 31982685
DOI: 10.1016/j.jpain.2020.01.003 -
The Cochrane Database of Systematic... Mar 2021High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review.
OBJECTIVES
To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches.
SELECTION CRITERIA
We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO/FiO) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO/FiO may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma.
AUTHORS' CONCLUSIONS
HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.
Topics: Acute Disease; Adult; Barotrauma; Bias; Critical Care; Hospital Mortality; Humans; Intubation; Length of Stay; Masks; Nasal Mucosa; Noninvasive Ventilation; Oxygen Inhalation Therapy; Patient Reported Outcome Measures; Pneumonia; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Insufficiency; Treatment Failure
PubMed: 33661521
DOI: 10.1002/14651858.CD010172.pub3 -
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 -
The Cochrane Database of Systematic... Nov 2022Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol... (Review)
Review
BACKGROUND
Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol deficiency and accumulation of various precursor molecules, mainly 7-dehydrocholesterol and 8-dehydrocholesterol. There is currently no cure for SLOS, with cholesterol supplementation being primarily a biochemical therapy of limited evidence. However, several anecdotal reports and preclinical studies have highlighted statins as a potential therapy for SLOS.
OBJECTIVES
To evaluate the effects of statins, either alone or in combination with other non-statin therapies (e.g. cholesterol, bile acid, or vitamin co-supplementation), compared to cholesterol supplementation alone or in combination with other non-statin therapies (e.g. bile acid or vitamin supplementation) on several important outcomes including overall survival, neurobehavioral features, and adverse effects in individuals with SLOS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, five other databases and three trials registers on 15 February 2022, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs with parallel or cross-over designs, and non-randomized studies of interventions (NRSIs) including non-randomized trials, cohort studies, and controlled before-and-after studies, were eligible for inclusion in this review if they met our prespecified inclusion criteria, i.e. involved human participants with biochemically or genetically diagnosed SLOS receiving statin therapy or cholesterol supplementation, or both.
DATA COLLECTION AND ANALYSIS
Two authors screened titles and abstracts and subsequently full-texts for all potentially-relevant references. Both authors independently extracted relevant data from included studies and assessed the risks of bias. We analyzed the data extracted from the included NRSIs and cohort studies separately from the data extracted from the single included RCT. We used a random-effects model to account for the inherent heterogeneity and methodological variation between these different study designs. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included six studies (61 participants with SLOS); one RCT (N = 18), three prospective NRSIs (N = 20), and two retrospective NRSIs (N = 22). Five studies included only children, and two limited their participant inclusion by disease severity. Overall, there were nearly twice as many males as females. All six studies compared add-on statin therapy to cholesterol supplementation alone. However, the dosages, formulations, and durations of treatment were highly variable across studies. We judged the RCT as having a high risk of bias due to missing data and selective reporting. All included NRSIs had a serious or critical overall risk of bias assessed by the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I). None of the included studies evaluated survival or reported quality of life (QoL). Only the included RCT formally assessed changes in the neurobehavioral manifestations of SLOS, and we are uncertain whether statin therapy improves this outcome (very low-certainty evidence). We are also uncertain whether the adverse events reported in the RCT were statin-related (very low-certainty evidence). In contrast, the adverse events reported in the NRSIs seem to be possibly due to statin therapy (risk ratio 13.00, 95% confidence interval 1.85 to 91.49; P = 0.01; low-certainty evidence), with only one of the NRSIs retrospectively mentioning changes in the irritability of two of their participants. We are uncertain whether statins affect growth based on the RCT or NRSI results (very low-certainty evidence). The RCT showed that statins may make little or no difference to plasma biomarker levels (low-certainty evidence), while we are uncertain of their effects on such parameters in the NRSIs (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Currently, there is no evidence on the potential effects of statin therapy in people with SLOS regarding survival or QoL, and very limited evidence on the effects on neurobehavioral manifestations. Likewise, current evidence is insufficient and of very low certainty regarding the effects of statins on growth parameters in children with SLOS and plasma or cerebrospinal fluid (CSF) levels of various disease biomarkers. Despite these limitations, current evidence seemingly suggests that statins may increase the risk of adverse reactions in individuals with SLOS receiving statins compared to those who are not. Given the insufficient evidence on potential benefits of statins in individuals with SLOS, and their potential for causing adverse reactions, anyone considering this therapy should take these findings into consideration. Future studies should address the highlighted gaps in evidence on the use of statins in individuals with SLOS by collecting prospective data on survival and performing serial standardized assessments of neurobehavioral features, QoL, anthropometric measures, and plasma and CSF biomarker levels after statin introduction. Future studies should also attempt to use consistent dosages, formulations and durations of cholesterol and statin therapy.
Topics: Child; Female; Humans; Male; Bile Acids and Salts; Cholesterol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Smith-Lemli-Opitz Syndrome; Vitamins; Randomized Controlled Trials as Topic; Cross-Over Studies
PubMed: 36373961
DOI: 10.1002/14651858.CD013521.pub2 -
Disability and Rehabilitation Dec 2020The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical...
The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical pain condition. The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane library and Web of Science. Two reviewers screened reports and extracted the data. A third reviewer acted as an arbiter. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and uncontrolled trials. Crossover and parallel-group designs were included. Risk of bias was assessed for all included studies. Thirteen clinical studies were included. The majority of studies investigated a sample of participants with chronic pain. Six were controlled trials and seven uncontrolled studies. Findings from controlled research suggest that interactive virtual reality may reduce pain associated with ankylosing spondylitis and post-mastectomy, but results are inconsistent for patients with neck pain. Findings from uncontrolled studies suggest that interactive virtual reality may reduce neuropathic limb pain, and phantom limb pain, but had no effect on nonspecific chronic back pain. There is a need for more rigorous randomized control trials in order to conclude on the effectiveness of the use of virtual reality for the management of pain.Implications for rehabilitationInteractive virtual reality has been increasingly used in the rehabilitation of painful conditions.Interactive virtual reality using exergames may promote distraction from painful exercises and reduce pain post-mastectomy and in patients with ankylosing spondylitis.Interactive virtual representation of limbs may reduce neuropathic and phantom limb pain.
Topics: Breast Neoplasms; Exercise Therapy; Female; Humans; Mastectomy; Pain Perception; Virtual Reality
PubMed: 31067135
DOI: 10.1080/09638288.2019.1610803 -
The Cochrane Database of Systematic... Oct 2021Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life.... (Review)
Review
BACKGROUND
Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life. Rehabilitation after stroke aims to reduce disability by facilitating recovery of impairment, activity, or participation. One aspect of stroke rehabilitation that may affect outcomes is the amount of time spent in rehabilitation, including minutes provided, frequency (i.e. days per week of rehabilitation), and duration (i.e. time period over which rehabilitation is provided). Effect of time spent in rehabilitation after stroke has been explored extensively in the literature, but findings are inconsistent. Previous systematic reviews with meta-analyses have included studies that differ not only in the amount provided, but also type of rehabilitation.
OBJECTIVES
To assess the effect of 1. more time spent in the same type of rehabilitation on activity measures in people with stroke; 2. difference in total rehabilitation time (in minutes) on recovery of activity in people with stroke; and 3. rehabilitation schedule on activity in terms of: a. average time (minutes) per week undergoing rehabilitation, b. frequency (number of sessions per week) of rehabilitation, and c. total duration of rehabilitation.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, eight other databases, and five trials registers to June 2021. We searched reference lists of identified studies, contacted key authors, and undertook reference searching using Web of Science Cited Reference Search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of adults with stroke that compared different amounts of time spent, greater than zero, in rehabilitation (any non-pharmacological, non-surgical intervention aimed to improve activity after stroke). Studies varied only in the amount of time in rehabilitation between experimental and control conditions. Primary outcome was activities of daily living (ADLs); secondary outcomes were activity measures of upper and lower limbs, motor impairment measures of upper and lower limbs, and serious adverse events (SAE)/death.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies, extracted data, assessed methodological quality using the Cochrane RoB 2 tool, and assessed certainty of the evidence using GRADE. For continuous outcomes using different scales, we calculated pooled standardised mean difference (SMDs) and 95% confidence intervals (CIs). We expressed dichotomous outcomes as risk ratios (RR) with 95% CIs.
MAIN RESULTS
The quantitative synthesis of this review comprised 21 parallel RCTs, involving analysed data from 1412 participants. Time in rehabilitation varied between studies. Minutes provided per week were 90 to 1288. Days per week of rehabilitation were three to seven. Duration of rehabilitation was two weeks to six months. Thirteen studies provided upper limb rehabilitation, five general rehabilitation, two mobilisation training, and one lower limb training. Sixteen studies examined participants in the first six months following stroke; the remaining five included participants more than six months poststroke. Comparison of stroke severity or level of impairment was limited due to variations in measurement. The risk of bias assessment suggests there were issues with the methodological quality of the included studies. There were 76 outcome-level risk of bias assessments: 15 low risk, 37 some concerns, and 24 high risk. When comparing groups that spent more time versus less time in rehabilitation immediately after intervention, we found no difference in rehabilitation for ADL outcomes (SMD 0.13, 95% CI -0.02 to 0.28; P = 0.09; I = 7%; 14 studies, 864 participants; very low-certainty evidence), activity measures of the upper limb (SMD 0.09, 95% CI -0.11 to 0.29; P = 0.36; I = 0%; 12 studies, 426 participants; very low-certainty evidence), and activity measures of the lower limb (SMD 0.25, 95% CI -0.03 to 0.53; P = 0.08; I = 48%; 5 studies, 425 participants; very low-certainty evidence). We found an effect in favour of more time in rehabilitation for motor impairment measures of the upper limb (SMD 0.32, 95% CI 0.06 to 0.58; P = 0.01; I = 10%; 9 studies, 287 participants; low-certainty evidence) and of the lower limb (SMD 0.71, 95% CI 0.15 to 1.28; P = 0.01; 1 study, 51 participants; very low-certainty evidence). There were no intervention-related SAEs. More time in rehabilitation did not affect the risk of SAEs/death (RR 1.20, 95% CI 0.51 to 2.85; P = 0.68; I = 0%; 2 studies, 379 participants; low-certainty evidence), but few studies measured these outcomes. Predefined subgroup analyses comparing studies with a larger difference of total time spent in rehabilitation between intervention groups to studies with a smaller difference found greater improvements for studies with a larger difference. This was statistically significant for ADL outcomes (P = 0.02) and activity measures of the upper limb (P = 0.04), but not for activity measures of the lower limb (P = 0.41) or motor impairment measures of the upper limb (P = 0.06).
AUTHORS' CONCLUSIONS
An increase in time spent in the same type of rehabilitation after stroke results in little to no difference in meaningful activities such as activities of daily living and activities of the upper and lower limb but a small benefit in measures of motor impairment (low- to very low-certainty evidence for all findings). If the increase in time spent in rehabilitation exceeds a threshold, this may lead to improved outcomes. There is currently insufficient evidence to recommend a minimum beneficial daily amount in clinical practice. The findings of this study are limited by a lack of studies with a significant contrast in amount of additional rehabilitation provided between control and intervention groups. Large, well-designed, high-quality RCTs that measure time spent in all rehabilitation activities (not just interventional) and provide a large contrast (minimum of 1000 minutes) in amount of rehabilitation between groups would provide further evidence for effect of time spent in rehabilitation.
Topics: Activities of Daily Living; Adult; Humans; Physical Therapy Modalities; Stroke; Stroke Rehabilitation; Upper Extremity
PubMed: 34695300
DOI: 10.1002/14651858.CD012612.pub2 -
The Cochrane Database of Systematic... Jul 2020Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and...
BACKGROUND
Asthma is a common chronic respiratory disease. People with asthma have inflammation of their airways that causes recurrent episodes of wheezing, breathlessness and chest tightness, with or without a cough. Statins possess multiple therapeutic effects, including lowering lipid levels in the blood. Statins are reported to have a potential role as an adjunct treatment in asthma. However, comprehensive evidence of the benefits and harms of using statins is required to facilitate decision making.
OBJECTIVES
To assess the benefits and harms of statins as an adjunct therapy for asthma in adults and children.
SEARCH METHODS
We searched for studies in the Cochrane Airways Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid SP and Embase Ovid SP, from their inception dates We handsearched the proceedings of major respiratory conferences. We also searched clinical trials registries for completed, ongoing and unpublished studies, and scanned the reference lists of included studies and relevant reviews to identify additional studies. The search is current to 7 February 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with a parallel-group design that assessed statins for at least 12 weeks' duration. We considered all participants with a clinical diagnosis of asthma to be eligible, regardless of age, sex, disease severity and previous or current treatment. We planned to include studies reported as full text, those published as abstract only, and unpublished data.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected the studies, extracted outcome data and intervention characteristics from included studies, and assessed risk of bias according to standard Cochrane methodological procedures. We resolved any disagreement through discussion.
MAIN RESULTS
We found only one trial involving a total of 60 people living with asthma. The trial compared the effect of atorvastatin with a placebo (dummy treatment containing lactose) in treating people with chronic asthma. The trial did not report data for the primary outcomes or adverse events. There was uncertainty about the relative effect on forced expiratory volume in one second (FEV) and peak expiratory flow (PEF) in the atorvastatin group compared with the placebo group. The study did not report serious adverse effects for the interventions. The included study had internal discrepancies in its reported data.
AUTHORS' CONCLUSIONS
The evidence was of very low certainty, so we are unable to draw conclusions about the effectiveness and safety of statins to treat asthma. High-quality RCTs are needed to assess the effect of statins on people with asthma. Well-designed multicentre trials with larger samples and longer duration of treatment are required, which assess outcomes such as adverse events, hospital utilisation and costs, to provide better quality evidence. Future studies that include subgroups of obese people with asthma are also required.
Topics: Anti-Asthmatic Agents; Asthma; Atorvastatin; Forced Expiratory Volume; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Peak Expiratory Flow Rate
PubMed: 32668027
DOI: 10.1002/14651858.CD013268.pub2 -
The Cochrane Database of Systematic... May 2020Prophylactic removal of asymptomatic disease-free impacted wisdom teeth is the surgical removal of wisdom teeth in the absence of symptoms and with no evidence of local...
BACKGROUND
Prophylactic removal of asymptomatic disease-free impacted wisdom teeth is the surgical removal of wisdom teeth in the absence of symptoms and with no evidence of local disease. Impacted wisdom teeth may be associated with pathological changes, such as pericoronitis, root resorption, gum and alveolar bone disease (periodontitis), caries and the development of cysts and tumours. When surgical removal is performed in older people, the risk of postoperative complications, pain and discomfort is increased. Other reasons to justify prophylactic removal of asymptomatic disease-free impacted third molars have included preventing late lower incisor crowding, preventing damage to adjacent structures such as the second molar or the inferior alveolar nerve, in preparation for orthognathic surgery, in preparation for radiotherapy or during procedures to treat people with trauma to the affected area. Removal of asymptomatic disease-free wisdom teeth is a common procedure, and researchers must determine whether evidence supports this practice. This review is an update of an review originally published in 2005 and previously updated in 2012 and 2016.
OBJECTIVES
To evaluate the effects of removal compared with retention (conservative management) of asymptomatic disease-free impacted wisdom teeth in adolescents and adults.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 10 May 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2019, Issue 4), MEDLINE Ovid (1946 to 10 May 2019), and Embase Ovid (1980 to 10 May 2019). The US National Institutes of Health Trials Registry (ClinicalTrials.gov)and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. .
SELECTION CRITERIA
We included randomised controlled trials (RCTs), with no restriction on length of follow-up, comparing removal (or absence) with retention (or presence) of asymptomatic disease-free impacted wisdom teeth in adolescents or adults. We also considered quasi-RCTs and prospective cohort studies for inclusion if investigators measured outcomes with follow-up of five years or longer.
DATA COLLECTION AND ANALYSIS
Eight review authors screened search results and assessed the eligibility of studies for inclusion according to the review inclusion criteria. Eight review authors independently and in duplicate conducted the risk of bias assessments. When information was unclear, we contacted the study authors for additional information.
MAIN RESULTS
This review update includes the same two studies that were identified in our previous version of the review: one RCT with a parallel-group design, which was conducted in a dental hospital setting in the United Kingdom, and one prospective cohort study, which was conducted in the private sector in the USA. Primary outcome No eligible studies in this review reported the effects of removal compared with retention of asymptomatic disease-free impacted wisdom teeth on health-related quality of life Secondary outcomes We found only low- to very low-certainty evidence of the effects of removal compared with retention of asymptomatic disease-free impacted wisdom teeth for a limited number of secondary outcome measures. One prospective cohort study, reporting data from a subgroup of 416 healthy male participants, aged 24 to 84 years, compared the effects of the absence (previous removal or agenesis) against the presence of asymptomatic disease-free impacted wisdom teeth on periodontitis and caries associated with the distal aspect of the adjacent second molar during a follow-up period of three to over 25 years. Very low-certainty evidence suggests that the presence of asymptomatic disease-free impacted wisdom teeth may be associated with increased risk of periodontitis affecting the adjacent second molar in the long term. In the same study, which is at serious risk of bias, there is insufficient evidence to demonstrate a difference in caries risk associated with the presence or absence of impacted wisdom teeth. One RCT with 164 randomised and 77 analysed adolescent participants compared the effect of extraction with retention of asymptomatic disease-free impacted wisdom teeth on dimensional changes in the dental arch after five years. Participants (55% female) had previously undergone orthodontic treatment and had 'crowded' wisdom teeth. No evidence from this study, which was at high risk of bias, was found to suggest that removal of asymptomatic disease-free impacted wisdom teeth has a clinically significant effect on dimensional changes in the dental arch. The included studies did not measure any of our other secondary outcomes: costs, other adverse events associated with retention of asymptomatic disease-free impacted wisdom teeth (pericoronitis, root resorption, cyst formation, tumour formation, inflammation/infection) and adverse effects associated with their removal (alveolar osteitis/postoperative infection, nerve injury, damage to adjacent teeth during surgery, bleeding, osteonecrosis related to medication/radiotherapy, inflammation/infection).
AUTHORS' CONCLUSIONS
Insufficient evidence is available to determine whether asymptomatic disease-free impacted wisdom teeth should be removed or retained. Although retention of asymptomatic disease-free impacted wisdom teeth may be associated with increased risk of periodontitis affecting adjacent second molars in the long term, the evidence is very low certainty. Well-designed RCTs investigating long-term and rare effects of retention and removal of asymptomatic disease-free impacted wisdom teeth, in a representative group of individuals, are unlikely to be feasible. In their continuing absence, high quality, long-term prospective cohort studies may provide valuable evidence in the future. Given the current lack of available evidence, patient values should be considered and clinical expertise used to guide shared decision-making with people who have asymptomatic disease-free impacted wisdom teeth. If the decision is made to retain these teeth, clinical assessment at regular intervals to prevent undesirable outcomes is advisable.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Diseases; Female; Humans; Male; Middle Aged; Molar, Third; Prospective Studies; Randomized Controlled Trials as Topic; Tooth Extraction; Tooth, Impacted; Watchful Waiting
PubMed: 32368796
DOI: 10.1002/14651858.CD003879.pub5 -
The Cochrane Database of Systematic... Nov 2022Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice... (Review)
Review
BACKGROUND
Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as insomnia, anxiety or depression. OBJECTIVES: To assess the effects of Ginkgo biloba for tinnitus in adults and children.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2022, Issue 6); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 June 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) recruiting adults and children with acute or chronic subjective tinnitus. We included studies where the intervention involved Ginkgo biloba and this was compared to placebo, no intervention, or education and information. Concurrent use of other medication or other treatment was acceptable if used equally in each group. Where an additional intervention was used equally in both groups, we analysed this as a separate comparison. The review included all courses of Ginkgo biloba, regardless of dose regimens or formulations, and for any duration of treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were tinnitus symptom severity measured as a global score on a multi-item tinnitus questionnaire and serious adverse effects (bleeding, seizures). Our secondary outcomes were tinnitus loudness (change in subjective perception), tinnitus intrusiveness, generalised depression, generalised anxiety, health-related quality of life and other adverse effects (gastrointestinal upset, headache, allergic reaction). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
This review included 12 studies (with a total of 1915 participants). Eleven studies compared the effects of Ginkgo biloba with placebo and one study compared the effects of Ginkgo biloba with hearing aids to hearing aids alone. All included studies were parallel-group RCTs. In general, risk of bias was high or unclear due to selection bias and poor reporting of allocation concealment and blinding of participants, personnel and outcome assessments. Due to heterogeneity in the outcomes measured and measurement methods used, only limited data pooling was possible. Ginkgo biloba versus placebo When we pooled data from two studies for the primary outcome tinnitus symptom severity, we found that Ginkgo biloba may have little to no effect (Tinnitus Handicap Inventory scores) at three to six months compared to placebo, but the evidence is very uncertain (mean difference (MD) -1.35 (scale 0 to 100), 95% confidence interval (CI) -8.26 to 5.55; 2 studies; 85 participants) (very low-certainty). Ginkgo biloba may result in little to no difference in the risk of bleeding or seizures, with no serious adverse effects reported in either group (4 studies; 1154 participants; low-certainty). For the secondary outcomes, one study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on tinnitus loudness measured with audiometric loudness matching at 12 weeks, but the evidence is very uncertain (MD -4.00 (scale -10 to 140 dB), 95% CI -13.33 to 5.33; 1 study; 73 participants) (very low-certainty). One study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on health-related quality of life measured with the Glasgow Health Status Inventory at three months (MD -0.58 (scale 0 to 100), 95% CI -4.67 to 3.51; 1 study; 60 participants) (low-certainty). Ginkgo biloba may not increase the frequency of other adverse effects (gastrointestinal upset, headache, allergic reaction) at three months compared to placebo (risk ratio 0.91, 95% CI 0.52 to 1.60; 4 studies; 1175 participants) (low-certainty). None of the studies reported the other secondary outcomes of tinnitus intrusiveness or changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety. Gingko biloba with concurrent intervention versus concurrent intervention only One study compared Ginkgo biloba with hearing aids to hearing aids only. It assessed the mean difference in the change in Tinnitus Handicap Inventory scores and tinnitus loudness using a 10-point visual analogue scale (VAS) at three months. The study did not report adverse effects, tinnitus intrusiveness, changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life. This was a single, very small study (22 participants) and for all outcomes the certainty of the evidence was very low. We were unable to draw meaningful conclusions from the numerical results.
AUTHORS' CONCLUSIONS
There is uncertainty about the benefits and harms of Ginkgo biloba for the treatment of tinnitus when compared to placebo. We were unable to draw meaningful conclusions regarding the benefits and harms of Ginkgo biloba when used with concurrent intervention (hearing aids). The certainty of the evidence for the reported outcomes, assessed using GRADE, ranged from low to very low. Future research into the effectiveness of Ginkgo biloba in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient-centred outcome measures for research in the field of tinnitus.
Topics: Adult; Child; Humans; Ginkgo biloba; Headache; Hypersensitivity; Seizures; Tinnitus; Randomized Controlled Trials as Topic
PubMed: 36383762
DOI: 10.1002/14651858.CD013514.pub2