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Cells Dec 2022To perform a systematic review of real-world outcomes for anti-CGRP-mAbs. (Review)
Review
OBJECTIVE
To perform a systematic review of real-world outcomes for anti-CGRP-mAbs.
METHODS
Following the PRISMA guidelines, we searched PubMed for real-world data of erenumab, galcanezumab, fremanezumab, or eptinezumab in patients with migraines.
RESULTS
We identified 134 publications (89 retrospective), comprising 10 pharmaco-epidemiologic and 83 clinic-based studies, 38 case reports, and 3 other articles. None of the clinic-based studies provided follow-up data over more than one year in more than 200 patients. Findings suggest that there are reductions in health insurance claims and days with sick-leave as well as better treatment adherence with anti-CGRP-mAbs. Effectiveness, reported in 77 clinic-based studies, was comparable to randomized controlled trials. A treatment pause was associated with an increase in migraine frequency, and switching to another antibody resulted in a better response in some of the patients. Adverse events and safety issues were addressed in 86 papers, including 24 single case reports.
CONCLUSION
Real-world data on anti-CGRP-mAbs are limited by retrospective data collection, small patient numbers, and short follow-up periods. The majority of papers seem to support good effectiveness and tolerability of anti-CGRP-mAbs in the real-world setting. There is an unmet need for large prospective real-world studies providing long-term follow-ups of patients treated with anti-CGRP-mAbs.
Topics: Humans; Calcitonin Gene-Related Peptide; Prospective Studies; Retrospective Studies; Antibodies, Monoclonal; Migraine Disorders
PubMed: 36611935
DOI: 10.3390/cells12010143 -
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 -
Physical Therapy May 2021Dry needling is a treatment technique used by clinicians to relieve symptoms in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Dry needling is a treatment technique used by clinicians to relieve symptoms in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. This systematic review's main objective was to assess the effectiveness of dry needling on headache pain intensity and related disability in patients with TTH, CGH, or migraine.
METHODS
Medline/PubMed, Scopus, Embase, PEDro, Web of Science, Ovid, Allied and Complementary Medicine Database/EBSCO, Cochrane Central Register of Controlled Clinical Trials, Google Scholar, and trial registries were searched until April 1, 2020, along with reference lists of eligible studies and related reviews. Randomized clinical trials or observational studies that compared the effectiveness of dry needling with any other interventions were eligible for inclusion. Three reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed to produce pooled-effect estimates (Morris dppc2) and their respective CIs.
RESULTS
Of 2715 identified studies, 11 randomized clinical trials were eligible for qualitative synthesis and 9 for meta-analysis. Only 4 trials were of high quality. Very low-quality evidence suggested that dry needling is not statistically better than other interventions for improving headache pain intensity in the short term in patients with TTH (SMD -1.27, 95% CI = -3.56 to 1.03, n = 230), CGH (SMD -0.41, 95% CI = -4.69 to 3.87, n = 104), or mixed headache (TTH and migraine; SMD 0.03; 95% CI = -0.42 to 0.48, n = 90). Dry needling provided significantly greater improvement in related disability in the short term in patients with TTH (SMD -2.28, 95% CI = -2.66 to -1.91, n = 160) and CGH (SMD -0.72, 95% CI = -1.09 to -0.34, n = 144). The synthesis of results showed that dry needling could significantly improve headache frequency, health-related quality of life, trigger point tenderness, and cervical range of motion in TTH and CGH.
CONCLUSIONS
Dry needling produces similar effects to other interventions for short-term headache pain relief, whereas dry needling seems to be better than other therapies for improvement in related disability in the short term.
IMPACT
Although further high-methodological quality studies are warranted to provide a more robust conclusion, our systematic review suggested that for every 1 or 2 patients with TTH treated by dry needling, 1 patient will likely show decreased headache intensity (number needed to treat [NNT] = 2; large effect) and improved related disability (NNT = 1; very large effect). In CGH, for every 3 or 4 patients treated by dry needling, 1 patient will likely exhibit decreased headache intensity (NNT = 4; small effect) and improved related disability (NNT = 3; medium effect).
Topics: Dry Needling; Humans; Migraine Disorders; Pain Measurement; Post-Traumatic Headache; Tension-Type Headache
PubMed: 33609358
DOI: 10.1093/ptj/pzab068 -
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 -
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 -
Cephalalgia : An International Journal... Dec 2022This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine in 2010.
METHODS
We systematically reviewed onabotulinumtoxinA observational data in chronic migraine published between 1 January 2010 and 31 March 2021. Random-effects models evaluated available data for primary and secondary endpoints defined in onabotulinumtoxinA pivotal trials at approximately 24 weeks and 52 weeks.
RESULTS
Of the 44 full-text eligible studies (29 prospective; 13 retrospective; 2 other), seven evaluated change from baseline (mean[confidence interval]) at ∼24 weeks and ∼52 weeks, respectively, for onabotulinumtoxinA in: : (-10.64 [-12.31, -8.97]; -10.32 [-14.92, -5.73]); (-7.40 [-13.04, -1.77]; overlapping CIs at 52 weeks); (-11.70 [-13.86, -9.54]); -11.80 [14.70, -8.90]); and (MSQ; 23.60 [CI: 21.56, 25.64]; 30.90 [CI: 28.29, 33.51]). At ∼24 weeks onabotulinumtoxinA showed of 44.74 [28.50, 60.99] and of 46.57% [29.50%, 63.65%]. A sensitivity analysis at study-end suggested durability of onabotulinumtoxinA effectiveness on MSQ.
CONCLUSION
The meta-analysis reflecting real-world practice broadly corroborated with evidence from pivotal and long-term open-label studies of onabotulinumtoxinA in chronic migraine preventive treatment.
Topics: Humans; Botulinum Toxins, Type A; Retrospective Studies; Prospective Studies; Treatment Outcome; Chronic Disease; Migraine Disorders; Headache; Acute Pain
PubMed: 36081276
DOI: 10.1177/03331024221123058 -
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 -
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