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European Neuropsychopharmacology : the... Nov 2023Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a... (Meta-Analysis)
Meta-Analysis Review
Psilocybin is increasingly studied for its antidepressant effect, but its optimal dosage for depression remains unclear. We conducted a systematic review and a dose-response meta-analysis to find the optimal dosage of psilocybin to reduce depression scores. Following our protocol (CRD 42022220190) multiple electronic databases were searched from their inception until February 2023, to identify double-blind randomized placebo-controlled (RCTs) fixed-dose trials evaluating the use of psilocybin for adult patients with primary or secondary depression. A one-stage dose-response meta-analysis with restricted cubic splines was used. Cochrane risk of bias was used to assess risk of bias. Our analysis included seven studies with a total of 489 participants. Among these, four studies focused on primary depression (N = 366), including one study with patients suffering from treatment-resistant depression. The remaining three studies examined secondary depression (N = 123). The determined 95% effective doses per day (ED95) were 8.92, 24.68, and 36.08 mg/70 kg for patients with secondary depression, primary depression, and both subgroups, respectively. We observed significant dose-response associations for all curves, each plateauing at different levels, except for the bell-shaped curve observed in the case of secondary depression. Additionally, we found significant dose-response associations for various side effects, including physical discomfort, blood pressure increase, nausea/vomiting, headache/migraine, and the risk of prolonged psychosis. In conclusion, we discovered specific ED95 values for different populations, indicating higher ED95 values for treatment-resistant depression, primary depression, and secondary depression groups. Further RCTs are necessary for each population to determine the optimal dosage, allowing for maximum efficacy while minimizing side effects.
Topics: Adult; Humans; Depression; Psilocybin; Antidepressive Agents; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 37557019
DOI: 10.1016/j.euroneuro.2023.07.011 -
Chiropractic & Manual Therapies Feb 2021A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders....
The global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders: a systematic review of the literature.
BACKGROUND
A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial.
OBJECTIVES
We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders.
GLOBAL SUMMIT
The Global Summit took place on September 14-15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence.
SYSTEMATIC REVIEW OF THE LITERATURE
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus.
RESULTS
We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report.
CONCLUSION
Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.
Topics: Asthma; Colic; Dysmenorrhea; Female; Humans; Hypertension; Manipulation, Spinal; Noncommunicable Diseases
PubMed: 33596925
DOI: 10.1186/s12998-021-00362-9 -
BMJ Open Jan 2021To determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the effects of coenzyme Q10 (CoQ10) for reduction in the severity, frequency of migraine attacks and duration of headache in adult patients with migraine.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, CENTRAL, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Psychological Information Database (PsycINFO) from inception till December 2019.
STUDY SELECTION
All randomised control trials comparing CoQ10 with placebo or used as an adjunct treatment included in this meta-analysis. Cross-over designs and controlled clinical trials were excluded.
DATA SYNTHESIS
Heterogeneity at face value by comparing populations, settings, interventions and outcomes were measured and statistical heterogeneity was assessed by means of the I statistic. The treatment effect for dichotomous outcomes were using risk ratios and risk difference, and for continuous outcomes, mean differences (MDs) or standardised mean difference; both with 95% CIs were used. Subgroup analyses were carried out for dosage of CoQ10 and if CoQ10 combined with another supplementation. Sensitivity analysis was used to investigate the impact risk of bias for sequence generation and allocation concealment of included studies.
RESULTS
Six studies with a total of 371 participants were included in the meta-analysis. There is no statistically significant reduction in severity of migraine headache with CoQ10 supplementation. CoQ10 supplementation reduced the duration of headache attacks compared with the control group (MD: -0.19; 95% CI: -0.27 to -0.11; random effects; I statistic=0%; p<0.00001). CoQ10 usage reduced the frequency of migraine headache compared with the control group (MD: -1.52; 95% CI: -2.40 to -0.65; random effects; I statistic=0%; p<0.001).
CONCLUSION
CoQ10 appears to have beneficial effects in reducing duration and frequency of migraine attack.
PROSPERO REGISTRATION NUMBER
CRD42019126127.
Topics: Adult; Dietary Supplements; Humans; Migraine Disorders; Ubiquinone
PubMed: 33402403
DOI: 10.1136/bmjopen-2020-039358 -
Journal of Integrative Neuroscience Aug 2023Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We aimed to review the efficacy of physical therapy and rehabilitation approaches for CM and their impact on quality of life (QoL) and disability.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) in adults with CM. The primary outcomes were changes in intensity, frequency, duration of headache, disability, and QoL. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Data synthesis and quantitative analysis were conducted on relevant studies.
RESULTS
Seven RCTs were included in the narrative review, and five of them were eligible for quantitative analysis. Aerobic exercise (AE), osteopathic manipulative treatment (OMT), occipital transcutaneous electrical stimulation (OTES), acupressure, hydrotherapy, instrument-assisted soft tissue mobilization (IASTM), facial proprioceptive neuromuscular facilitation (FPNF), and connective tissue massage (CTM) were used in CM. AE combined with pharmacological therapy reduced the frequency, duration, and intensity of headache. OMT combined with medication improved QoL and reduced disability, intensity of pain, and migraine days per month. Hydrotherapy combined with medication also resulted in improvements in the intensity of headache, frequency, and overall QoL. IASTM and OTES reduced the intensity of headache, alleviated neck pain, and improved QoL, although there were conflicting findings following OTES alone on disability and intensity of headache. Both FPNF and CTM reduced the intensity of headache. Acupressure as an adjunct to medication did not show additional benefits on the intensity of headache and QoL. Quantitative analysis of the data showed that manual physical therapy combined with medication reduced the intensity of headache ( = 0.0796), and manual or AE combined with medication reduced the headache days per month ( = 0.047).
CONCLUSIONS
A limited number of RCTs investigating the efficacy of physical therapy and rehabilitation approaches show promise in improving headache symptoms, reducing disability, and enhancing QoL in CM. Meta-analysis of the data also supported favorable outcomes for both intensity and headache days per month. Further research is needed to better understand the efficacy, optimal duration, and safety of physical therapy and rehabilitation approaches for CM, and to explore alternative interventions.
Topics: Adult; Humans; Physical Therapy Modalities; Migraine Disorders; Headache; Pain; Databases, Factual
PubMed: 37735140
DOI: 10.31083/j.jin2205126 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4 -
Tremor and Other Hyperkinetic Movements... 2023Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1... (Review)
Review
BACKGROUND
Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in and . EA3-8 are reported in rare families. Advances in genetic testing have broadened the and phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders. Together, these can pose diagnostic challenges for neurologists.
METHODS
A systematic literature review was performed in October 2022 for 'episodic ataxia' and 'paroxysmal ataxia', restricted to publications in the last 10 years to focus on recent clinical advances. Clinical, genetic, and treatment characteristics were summarized.
RESULTS
EA1 and EA2 phenotypes have further broadened. In particular, EA2 may be accompanied by other paroxysmal disorders of childhood with chronic neuropsychiatric features. New treatments for EA2 include dalfampridine and fampridine, in addition to 4-aminopyridine and acetazolamide. There are recent proposals for EA9-10. EA may also be caused by gene mutations associated with chronic ataxias (), epilepsy syndromes (), GLUT-1, mitochondrial disorders (), metabolic disorders (Maple syrup urine disease, Hartnup disease, type I citrullinemia, thiamine and biotin metabolism defects), and others. Secondary causes of EA are more commonly encountered than primary EA (vascular, inflammatory, toxic-metabolic). EA can be misdiagnosed as migraine, peripheral vestibular disorders, anxiety, and functional symptoms. Primary and secondary EA are frequently treatable which should prompt a search for the cause.
DISCUSSION
EA may be overlooked or misdiagnosed for a variety of reasons, including phenotype-genotype variability and clinical overlap between primary and secondary causes. EA is highly treatable, so it is important to consider in the differential diagnosis of paroxysmal disorders. Classical EA1 and EA2 phenotypes prompt single gene test and treatment pathways. For atypical phenotypes, next generation genetic testing can aid diagnosis and guide treatment. Updated classification systems for EA are discussed which may assist diagnosis and management.
Topics: Humans; Ataxia; Cerebellar Ataxia; Acetazolamide; Mutation
PubMed: 37008993
DOI: 10.5334/tohm.747 -
Chiropractic & Manual Therapies 2019Headache is the most common neurological symptoms worldwide, as over 90% of people have noted at least one headache during their lifetime. Tension-type headaches,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Headache is the most common neurological symptoms worldwide, as over 90% of people have noted at least one headache during their lifetime. Tension-type headaches, cervicogenic headaches, and migraines are common types of headache which can have a significant impact on social, physical, and occupational functioning. Therapeutic management of headaches mainly includes physical therapy and pharmacological interventions. Dry needling is a relatively new therapeutic approach that uses a thin filiform needle without injectate to penetrate the skin and stimulate underlying tissues for the management of neuromusculoskeletal pain and movement impairments.The main objective of this systematic review and meta-analysis is to evaluate the effectiveness of dry needling in comparison to other interventions on pain and disability in patients with tension-type headache, cervicogenic headache, and migraine.
METHODS/DESIGN
We will focus on clinical trials with concurrent control group(s) and comparative observational studies assessing the effect of dry needling in patients with tension-type headache, cervicogenic headache, and migraine. Electronic databases from relevant fields of research (PubMed/ Medline, Scopus, Embase®, PEDro, Web of Science, Ovid, AMED, CENTRAL, and Google Scholar) will be searched from inception to June 2019 using defined search terms. No restrictions for language of publication or geographic location will be applied. Moreover, grey literature, citation tracking, and reference lists scanning of the selected studies will be searched manually. Primary outcomes of this study are pain intensity and disability, and secondary outcomes are cervical spine ROM, frequency of headaches, health-related quality of life, and TrPs tenderness. Studies will be selected by three independent reviewers based on prespecified eligibility criteria. Three reviewers will independently extract data in each eligible study using a pre-piloted Microsoft Excel data extraction form. The assessment of risk of bias will be implemented using the Cochrane Back and Neck Review Group 13-item criteria and NOS. Direct meta-analysis will be performed using a fixed or random effects model to estimate effect size such as standardized mean difference (Morris's ) and 95% confidence intervals. Statistical heterogeneity will also be evaluated using the statistic and the χ test. All meta-analyses will be performed using Stata V.11 and V.14 softwares. The overall quality of the evidence for the primary outcomes will be assessed using GRADE.
DISCUSSION
All analyses in this study will be based on the previous published papers. Therefore, ethical approval and patient consent are not required. The findings of this study will provide important information on the value of dry needling for the management of tension-type headache, cervicogenic headache, and migraine.
TRIAL REGISTRATION
PROSPERO registration number: CRD42019124125.
Topics: Acupuncture Therapy; Adult; Disabled Persons; Dry Needling; Female; Humans; Male; Migraine Disorders; Post-Traumatic Headache; Randomized Controlled Trials as Topic; Research Design; Tension-Type Headache
PubMed: 31572570
DOI: 10.1186/s12998-019-0266-7 -
Cephalalgia : An International Journal... Mar 2023We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. (Meta-Analysis)
Meta-Analysis
Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature.
BACKGROUND
We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks.
METHODS
MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines.
RESULTS
Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan.
CONCLUSION
Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself. CRD42022308224.
Topics: Adult; Humans; Network Meta-Analysis; Double-Blind Method; Migraine Disorders; Treatment Outcome
PubMed: 36786357
DOI: 10.1177/03331024231151419 -
Health Technology Assessment... Feb 2020Splints are a non-invasive, reversible management option for temporomandibular disorders or bruxism. The clinical effectiveness and cost-effectiveness of splints remain...
BACKGROUND
Splints are a non-invasive, reversible management option for temporomandibular disorders or bruxism. The clinical effectiveness and cost-effectiveness of splints remain uncertain.
OBJECTIVES
The objectives were to evaluate the clinical effectiveness and cost-effectiveness of splints for patients with temporomandibular disorders or bruxism. This evidence synthesis compared (1) all types of splint versus no/minimal treatment/control splints and (2) prefabricated versus custom-made splints, for the primary outcomes, which were pain (temporomandibular disorders) and tooth wear (bruxism).
REVIEW METHODS
Four databases, including MEDLINE and EMBASE, were searched from inception until 1 October 2018 for randomised clinical trials. The searches were conducted on 1 October 2018. Cochrane review methods (including risk of bias) were used for the systematic review. Standardised mean differences were pooled for the primary outcome of pain, using random-effects models in temporomandibular disorder patients. A Markov cohort, state-transition model, populated using current pain and Characteristic Pain Intensity data, was used to estimate the incremental cost-effectiveness ratio for splints compared with no splint, from an NHS perspective over a lifetime horizon. A value-of-information analysis identified future research priorities.
RESULTS
Fifty-two trials were included in the systematic review. The evidence identified was of very low quality with unclear reporting by temporomandibular disorder subtype. When all subtypes were pooled into one global temporomandibular disorder group, there was no evidence that splints reduced pain [standardised mean difference (at up to 3 months) -0.18, 95% confidence interval -0.42 to 0.06; substantial heterogeneity] when compared with no splints or a minimal intervention. There was no evidence that other outcomes, including temporomandibular joint noises, decreased mouth-opening, and quality of life, improved when using splints. Adverse events were generally not reported, but seemed infrequent when reported. The most plausible base-case incremental cost-effectiveness ratio was uncertain and driven by the lack of clinical effectiveness evidence. The cost-effectiveness acceptability curve showed splints becoming more cost-effective at a willingness-to-pay threshold of ≈£6000, but the probability never exceeded 60% at higher levels of willingness to pay. Results were sensitive to longer-term extrapolation assumptions. A value-of-information analysis indicated that further research is required. There were no studies measuring tooth wear in patients with bruxism. One small study looked at pain and found a reduction in the splint group [mean difference (0-10 scale) -2.01, 95% CI -1.40 to -2.62; very low-quality evidence]. As there was no evidence of a difference between splints and no splints, the second objective became irrelevant.
LIMITATIONS
There was a large variation in the diagnostic criteria, splint types and outcome measures used and reported. Sensitivity analyses based on these limitations did not indicate a reduction in pain.
CONCLUSIONS
The very low-quality evidence identified did not demonstrate that splints reduced pain in temporomandibular disorders as a group of conditions. There is insufficient evidence to determine whether or not splints reduce tooth wear in patients with bruxism. There remains substantial uncertainty surrounding the most plausible incremental cost-effectiveness ratio.
FUTURE WORK
There is a need for well-conducted trials to determine the clinical effectiveness and cost-effectiveness of splints in patients with carefully diagnosed and subtyped temporomandibular disorders, and patients with bruxism, using agreed measures of pain and tooth wear.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42017068512.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 7. See the NIHR Journals Library website for further project information.
Topics: Adolescent; Adult; Bruxism; Child; Cost-Benefit Analysis; Humans; Markov Chains; Models, Econometric; Pain Measurement; Randomized Controlled Trials as Topic; Splints; State Medicine; Technology Assessment, Biomedical; Temporomandibular Joint Disorders; Young Adult
PubMed: 32065109
DOI: 10.3310/hta24070 -
The Cochrane Database of Systematic... Feb 2023Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been hypothesised that the use of micro-organisms, such as probiotics and synbiotics (a mixture of probiotics and prebiotics), might change the composition of bacterial colonies in the bowel and reduce inflammation, as well as promote normal gut physiology and reduce functional symptoms.
OBJECTIVES
To assess the efficacy and safety of probiotics in the treatment of functional abdominal pain disorders in children.
SEARCH METHODS
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and two clinical trials registers from inception to October 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compare probiotic preparations (including synbiotics) to placebo, no treatment or any other interventional preparation in patients aged between 4 and 18 years of age with a diagnosis of functional abdominal pain disorder according to the Rome II, Rome III or Rome IV criteria.
DATA COLLECTION AND ANALYSIS
The primary outcomes were treatment success as defined by the primary studies, complete resolution of pain, improvement in the severity of pain and improvement in the frequency of pain. Secondary outcomes included serious adverse events, withdrawal due to adverse events, adverse events, school performance or change in school performance or attendance, social and psychological functioning or change in social and psychological functioning, and quality of life or change in quality life measured using any validated scoring tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI.
MAIN RESULTS
We included 18 RCTs assessing the effectiveness of probiotics and synbiotics in reducing the severity and frequency of pain, involving a total of 1309 patients. Probiotics may achieve more treatment success when compared with placebo at the end of the treatment, with 50% success in the probiotic group versus 33% success in the placebo group (RR 1.57, 95% CI 1.05 to 2.36; 554 participants; 6 studies; I = 70%; low-certainty evidence). It is not clear whether probiotics are more effective than placebo for complete resolution of pain, with 42% success in the probiotic group versus 27% success in the placebo group (RR 1.55, 95% CI 0.94 to 2.56; 460 participants; 6 studies; I = 70%; very low-certainty evidence). We judged the evidence to be of very low certainty due to high inconsistency and risk of bias. We were unable to draw meaningful conclusions from our meta-analyses of the pain severity and pain frequency outcomes due to very high unexplained heterogeneity leading to very low-certainty evidence. None of the included studies reported serious adverse events. Meta-analysis showed no difference in withdrawals due to adverse events between probiotics (1/275) and placebo (1/269) (RR 1.00, 95% CI 0.07 to 15.12). The results were identical for the total patients with any reported adverse event outcome. However, these results are of very low certainty due to imprecision from the very low numbers of events and risk of bias. Synbiotics may result in more treatment success at study end when compared with placebo, with 47% success in the probiotic group versus 35% success in the placebo group (RR 1.34, 95% CI 1.03 to 1.74; 310 participants; 4 studies; I = 0%; low certainty). One study used Bifidobacterium coagulans/fructo-oligosaccharide, one used Bifidobacterium lactis/inulin, one used Lactobacillus rhamnosus GG/inulin and in one study this was not stated). Synbiotics may result in little difference in complete resolution of pain at study end when compared with placebo, with 52% success in the probiotic group versus 32% success in the placebo group (RR 1.65, 95% CI 0.97 to 2.81; 131 participants; 2 studies; I = 18%; low-certainty evidence). We were unable to draw meaningful conclusions from our meta-analyses of pain severity or frequency of pain due to very high unexplained heterogeneity leading to very low-certainty evidence. None of the included studies reported serious adverse events. Meta-analysis showed little to no difference in withdrawals due to adverse events between synbiotics (8/155) and placebo (1/147) (RR 4.58, 95% CI 0.80 to 26.19), or in any reported adverse events (3/96 versus 1/93, RR 2.88, 95% CI 0.32 to 25.92). These results are of very low certainty due to imprecision from the very low numbers of events and risk of bias. There were insufficient data to analyse by subgroups of specific functional abdominal pain syndrome (irritable bowel syndrome, functional dyspepsia, abdominal migraine, functional abdominal pain - not otherwise specified) or by specific strain of probiotic. There was insufficient evidence on school performance or change in school performance/attendance, social and psychological functioning, or quality of life to draw conclusions about the effects of probiotics or synbiotics on these outcomes.
AUTHORS' CONCLUSIONS
The results from this review demonstrate that probiotics and synbiotics may be more efficacious than placebo in achieving treatment success, but the evidence is of low certainty. The evidence demonstrates little to no difference between probiotics or synbiotics and placebo in complete resolution of pain. We were unable to draw meaningful conclusions about the impact of probiotics or synbiotics on the frequency and severity of pain as the evidence was all of very low certainty due to significant unexplained heterogeneity or imprecision. There were no reported cases of serious adverse events when using probiotics or synbiotics amongst the included studies, although a review of RCTs may not be the best context to assess long-term safety. The available evidence on adverse effects was of very low certainty and no conclusions could be made in this review. Safety will always be a priority in paediatric populations when considering any treatment. Reporting of all adverse events, adverse events needing withdrawal, serious adverse events and, particularly, long-term safety outcomes are vital to meaningfully move forward the evidence base in this field. Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies to confirm the safety of specific strains not yet investigated and studies to investigate long-term follow-up of patients are both warranted.
Topics: Humans; Child; Child, Preschool; Adolescent; Inulin; Probiotics; Irritable Bowel Syndrome; Abdominal Pain; Treatment Outcome
PubMed: 36799531
DOI: 10.1002/14651858.CD012849.pub2