-
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 -
The Cochrane Database of Systematic... Nov 2015Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-prescription (over-the-counter, or OTC) analgesics (painkillers) are used frequently. They are available in various brands, package sizes, formulations, and dose. They can be used for a range of different types of pain, but this overview reports on how well they work for acute pain (pain of short duration, usually with rapid onset). Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain.
OBJECTIVES
To examine published Cochrane reviews for information about the efficacy of pain medicines available without prescription using data from acute postoperative pain.
METHODS
We identified OTC analgesics available in the UK, Australia, Canada, and the USA by examining online pharmacy websites. We also included some analgesics (diclofenac potassium, dexketoprofen, dipyrone) of importance in parts of the world, but not currently available in these jurisdictions.We identified systematic reviews by searching the Cochrane Database of Systematic Reviews (CDSR) on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. From individual reviews we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also calculated the success rate to achieve at least 50% of maximum pain relief. We also examined the number of participants experiencing any adverse event, and whether the incidence was different from placebo.
MAIN RESULTS
We found information on 21 different OTC analgesic drugs, doses, and formulations, using information from 10 Cochrane reviews, supplemented by information from one non-Cochrane review with additional information on ibuprofen formulations (high quality evidence). The lowest (best) NNT values were for combinations of ibuprofen plus paracetamol, with NNT values below 2. Analgesics with values close to 2 included fast acting formulations of ibuprofen 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg. Combinations of ibuprofen plus paracetamol had success rates of almost 70%, with dipyrone 500 mg, fast acting ibuprofen formulations 200 mg and 400 mg, ibuprofen 200 mg plus caffeine 100 mg, and diclofenac potassium 50 mg having success rates above 50%. Paracetamol and aspirin at various doses had NNT values of 3 or above, and success rates of 11% to 43%. We found no information on many of the commonly available low dose codeine combinations.The proportion of participants experiencing an adverse event were generally not different from placebo, except for aspirin 1000 mg and (barely) ibuprofen 200 mg plus caffeine 100 mg. For ibuprofen plus paracetamol, adverse event rates were lower than with placebo.
AUTHORS' CONCLUSIONS
There is a body of reliable evidence about the efficacy of some of the most commonly available drugs and doses widely available without prescription. The postoperative pain model is predominantly pain after third molar extraction, which is used as the industry model for everyday pain. The proportion of people with acute pain who get good pain relief with any of them ranges from around 70% at best to less than 20% at worst; low doses of some drugs in fast acting formulations were among the best. Adverse events were generally no different from placebo. Consumers can make an informed choice based on this knowledge, together with availability and price. Headache and migraine were not included in this overview.
Topics: Acute Pain; Administration, Oral; Analgesics; Humans; Nonprescription Drugs; Numbers Needed To Treat; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 26544675
DOI: 10.1002/14651858.CD010794.pub2 -
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... Aug 2018Long-term physical conditions affect 10% to 12% of children and adolescents worldwide; these individuals are at greater risk of developing psychological problems,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Long-term physical conditions affect 10% to 12% of children and adolescents worldwide; these individuals are at greater risk of developing psychological problems, particularly anxiety and depression. Access to face-to-face treatment for such problems is often limited, and available interventions usually have not been tested with this population. As technology improves, e-health interventions (delivered via digital means, such as computers and smart phones and ranging from simple text-based programmes through to multimedia and interactive programmes, serious games, virtual reality and biofeedback programmes) offer a potential solution to address the psychological needs of this group of young people.
OBJECTIVES
To assess the effectiveness of e-health interventions in comparison with attention placebos, psychological placebos, treatment as usual, waiting-list controls, or non-psychological treatments for treating anxiety and depression in children and adolescents with long-term physical conditions.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Group's Controlled Trials Register (CCMDTR to May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2017), Web of Science (1900 - 18 August 2016, updated 31 August 2017) and Ovid MEDLINE, Embase, PsycINFO (cross-search 2016 to 18 Aug 2017). We hand-searched relevant conference proceedings, reference lists of included articles, and the grey literature to May 2016. We also searched international trial registries to identify unpublished or ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-randomised trials, and cross-over trials of e-health interventions for treating any type of long-term physical condition in children and adolescents (aged 0 to 18 years), and that measured changes in symptoms or diagnoses of anxiety, depression, or subthreshold depression. We defined long-term physical conditions as those that were more than three-months' duration. We assessed symptoms of anxiety and depression using patient- or clinician-administered validated rating scales based on DSM III, IV or 5 (American Psychological Association 2013), or ICD 9 or 10 criteria (World Health Organization 1992). Formal depressive and anxiety disorders were diagnosed using structured clinical interviews. Attention placebo, treatment as usual, waiting list, psychological placebo, and other non-psychological therapies were eligible comparators.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed titles, abstracts, and full-text articles; discrepancies were resolved through discussion or addressed by a third author. When available, we used odds ratio (OR) to compare dichotomous data and standardised mean differences (SMD) to analyse continuous data, both with 95% confidence intervals (CI). We undertook meta-analysis when treatments, participants, and the underlying clinical question were adequately similar. Otherwise, we undertook a narrative analysis.
MAIN RESULTS
We included five trials of three interventions (Breathe Easier Online, Web-MAP, and multimodal cognitive behavioural therapy (CBT)), which included 463 participants aged 10 to 18 years. Each trial contributed to at least one meta-analysis. Trials involved children and adolescents with long-term physical conditions, such as chronic headache (migraine, tension headache, and others), chronic pain conditions (abdominal, musculoskeletal, and others), chronic respiratory illness (asthma, cystic fibrosis, and others), and symptoms of anxiety or depression. Participants were recruited from community settings and hospital clinics in high income countries.For the primary outcome of change in depression symptoms versus any control, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.06, 95% CI -0.35 to 0.23; five RCTs, 441 participants). For the primary outcome of change in anxiety symptoms versus any comparator, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.07, 95% CI -0.29 to 0.14; two RCTs, 324 participants). For the primary outcome of treatment acceptability, there was very low-quality evidence that e-health interventions were less acceptable than any comparator (SMD 0.46, 95% CI 0.23 to 0.69; two RCTs, 304 participants).For the secondary outcome of quality of life, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.83, 95% CI -1.53 to -0.12; one RCT, 34 participants). For the secondary outcome of functioning, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.08, 95% CI -0.33 to 0.18; three RCTs, 368 participants). For the secondary outcome of status of long-term physical condition, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD 0.06, 95% CI -0.12 to 0.24; five RCTs, 463 participants).The risk of selection bias was considered low in most trials. However, the risk of bias due to inadequate blinding of participants or outcome assessors was considered unclear or high in all trials. Only one study had a published protocol; two trials had incomplete outcome data. All trials were conducted by the intervention developers, introducing another possible bias. No adverse effects were reported by any authors.
AUTHORS' CONCLUSIONS
At present, the field of e-health interventions for the treatment of anxiety or depression in children and adolescents with long-term physical conditions is limited to five low quality trials. The very low-quality of the evidence means the effects of e-health interventions are uncertain at this time, especially in children aged under 10 years.Although it is too early to recommend e-health interventions for this clinical population, given their growing number, and the global improvement in access to technology, there appears to be room for the development and evaluation of acceptable and effective technologically-based treatments to suit children and adolescents with long-term physical conditions.
Topics: Adolescent; Anxiety; Breathing Exercises; Child; Chronic Disease; Cognitive Behavioral Therapy; Depression; Humans; Randomized Controlled Trials as Topic; Telemedicine; Treatment Outcome
PubMed: 30110718
DOI: 10.1002/14651858.CD012489.pub2 -
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 -
Frontiers in Nutrition 2023Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising...
INTRODUCTION
Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising approach is ketogenic therapy, which replaces the brain's glucose fuel source with ketone bodies, potentially reducing the frequency or severity of headaches.
AIM
This study aims to conduct a systematic review of the scientific literature on the impact of ketosis on migraine, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.
RESULTS
After a careful selection process and bias evaluation, 10 articles were included in the review, primarily from Italy. The bias assessment indicated that 50% of the selected articles had a low risk of bias in all domains, with the randomization process being the most problematic domain. Unfortunately, the evaluation of ketosis was inconsistent between articles, with some assessing ketonuria, some assessing ketonemia, and some not assessing ketosis levels at all. Therefore, no association could be made between the level of ketosis and the prevention or reduction of migraine attacks. The ketogenic therapies tested in migraine treatments included the very low-calorie ketogenic diet (VLCKD, = 4), modified Atkins diet (MAD, = 3), classic ketogenic diet (cKDT, = 2), and the administration of an exogenous source of beta-hydroxybutyrate (BHB). The meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect ( = 9.07, < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, = 0.03; , 67.4%), regardless of the type of endogenous or exogenous induction of ketosis.
CONCLUSION
The initial findings of this study suggest that metabolic ketogenic therapy may provide some benefit in treating migraines and encourage further studies, especially randomized clinical trials with appropriate and standardized methodologies. The review strongly recommends the use of the adequate measurement of ketone levels during ketogenic therapy to monitor adherence to the treatment and improve knowledge of the relationship between ketone bodies and efficacy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.
PubMed: 37377485
DOI: 10.3389/fnut.2023.1204700 -
The Cochrane Database of Systematic... Apr 2019Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and... (Review)
Review
BACKGROUND
Chronic pain, considered to be pain lasting more than three months, is a common and often difficult to treat condition that can significantly impact upon function and quality of life. Treatment typically includes pharmacological and non-pharmacological approaches. Transcutaneous electrical nerve stimulation (TENS) is an adjunct non-pharmacological treatment commonly recommended by clinicians and often used by people with pain.
OBJECTIVES
To provide an overview of evidence from Cochrane Reviews of the effectiveness of TENS to reduce pain in adults with chronic pain (excluding headache or migraine).To provide an overview of evidence from Cochrane Reviews of the safety of TENS when used to reduce pain in adults with chronic pain (excluding headache or migraine).To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain (excluding headache or migraine) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting.To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain (excluding headache or migraine) with a view to recommending strategies to reduce any uncertainty.
METHODS
Search methodsWe searched the Cochrane Database of Systematic Reviews (CDSR), in the Cochrane Library, across all years up to Issue 11 of 12, 2018.Selection of reviewsTwo authors independently screened the results of the electronic search by title and abstract against inclusion/exclusion criteria. We included all Cochrane Reviews of randomised controlled trials (RCTs) assessing the effectiveness of TENS in people with chronic pain. We included reviews if they investigated the following: TENS versus sham; TENS versus usual care or no treatment/waiting list control; TENS plus active intervention versus active intervention alone; comparisons between different types of TENS; or TENS delivered using different stimulation parameters.Data extraction and analysisTwo authors independently extracted relevant data, assessed review quality using the AMSTAR checklist and applied GRADE judgements where required to individual reviews. Our primary outcomes included pain intensity and nature/incidence of adverse effects; our secondary outcomes included disability, health-related quality of life, analgesic medication use and participant global impression of change.
MAIN RESULTS
We included nine reviews investigating TENS use in people with defined chronic pain or in people with chronic conditions associated with ongoing pain. One review investigating TENS for phantom or stump-associated pain in people following amputation did not have any included studies. We therefore extracted data from eight reviews which represented 51 TENS-related RCTs representing 2895 TENS-comparison participants entered into the studies.The included reviews followed consistent methods and achieved overall high scores on the AMSTAR checklist. The evidence reported within each review was consistently rated as very low quality. Using review authors' assessment of risk of bias, there were significant methodological limitations in included studies; and for all reviews, sample sizes were consistently small (the majority of studies included fewer than 50 participants per group).Six of the eight reviews presented a narrative synthesis of included studies. Two reviews reported a pooled analysis.Primary and secondary outcomes One review reported a beneficial effect of TENS versus sham therapy at reducing pain intensity on a 0 to 10 scale (MD -1.58, 95% CI -2.08 to -1.09, P < 0.001, I² = 29%, P = 0.22, 5 studies, 207 participants). However the quality of the evidence was very low due to significant methodological limitations and imprecision. A second review investigating pain intensity performed a pooled analysis by combining studies that compared TENS to sham with studies that compared TENS to no intervention (SMD -0.85, 95% CI -1.36 to -0.34, P = 0.001, I² = 83%, P < 0.001). This pooled analysis was judged as offering very low quality evidence due to significant methodological limitations, large between-trial heterogeneity and imprecision. We considered the approach of combining sham and no intervention data to be problematic since we would predict these different comparisons may be estimating different true effects. All remaining reviews also reported pain intensity as an outcome measure; however the data were presented in narrative review form only.Due to methodological limitation and lack of useable data, we were unable to offer any meaningful report on the remaining primary outcome regarding nature/incidence of adverse effects, nor for the remaining secondary outcomes: disability, health-related quality of life, analgesic medication use and participant global impression of change for any comparisons.We found the included reviews had a number of inconsistencies when evaluating the evidence from TENS studies. Approaches to assessing risk of bias around the participant, personnel and outcome-assessor blinding were perhaps the most obvious area of difference across included reviews. We also found wide variability in terms of primary and secondary outcome measures, and inclusion/exclusion criteria for studies varied with respect to including studies which assessed immediate effects of single interventions.
AUTHORS' CONCLUSIONS
We found the methodological quality of the reviews was good, but quality of the evidence within them was very low. We were therefore unable to conclude with any confidence that, in people with chronic pain, TENS is harmful, or beneficial for pain control, disability, health-related quality of life, use of pain relieving medicines, or global impression of change. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment in people with chronic pain.
Topics: Chronic Pain; Humans; Pain Management; Pain Measurement; Systematic Reviews as Topic; Transcutaneous Electric Nerve Stimulation; Treatment Outcome
PubMed: 30941745
DOI: 10.1002/14651858.CD011890.pub3 -
European Journal of Neurology Mar 2022Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial... (Review)
Review
BACKGROUND AND PURPOSE
Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial fibrillation, which is a relevant risk factor for stroke.
METHODS
PubMed was searched for 'migraine' AND 'atrial fibrillation' and selected original investigations on the association of migraine and atrial fibrillation for our analysis. Articles without original data, such as guidelines, narrative reviews, editorials and others, were excluded.
RESULTS
In all, 109 publications were found. Twenty-two were included and analysed for this review. The population-based Atherosclerosis Risk in Communities study showed a significant association of migraine with visual aura and incident atrial fibrillation (hazard ratio 1.30, 95% confidence interval 1.03-1.62, p = 0.02), but not for migraine without aura, compared to non-headache persons after multivariable adjustment for vascular risk factors. An even larger population-based study in Denmark confirmed this association (odds ratio 1.25, 95% confidence interval 1.16-1.36). Studies investigating patients with ischaemic stroke and migraine are methodologically insufficient and provide contradictory results. Ablation therapy for atrial fibrillation in patients with migraine might reduce migraine attacks, but transient post-ablation new-onset migraine-like headaches in persons without a history of migraine have also been reported.
CONCLUSION
Population-based studies indicate a significant association of migraine with aura and atrial fibrillation. In practical terms, screening for atrial fibrillation in patients who have a long history of migraine might be reasonable, whereas in patients with stroke or other disorders and migraine extensive screening for atrial fibrillation should be performed as in all patients without migraine.
Topics: Atrial Fibrillation; Brain Ischemia; Humans; Migraine Disorders; Migraine with Aura; Risk Factors; Stroke
PubMed: 34826198
DOI: 10.1111/ene.15198