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Clinical Gastroenterology and... May 2022There are several licensed drugs for irritable bowel syndrome (IBS) that have proven efficacy in randomized controlled trials (RCTs), but placebo response rates are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
There are several licensed drugs for irritable bowel syndrome (IBS) that have proven efficacy in randomized controlled trials (RCTs), but placebo response rates are high. We conducted a systematic review and meta-analysis of licensed drugs to estimate magnitude of placebo response rate according to Food and Drug Administration (FDA)-recommended endpoints and to assess how this varies with stringency of the endpoint used to define response.
METHODS
We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through January 2021) to identify RCTs comparing licensed drugs with placebo in adult IBS patients. Studies assessed efficacy according to at least one of composite response, abdominal pain response, or stool response. Data were extracted as intention-to-treat analyses, with dropouts assumed to be treatment failures and pooled using a random-effects model.
RESULTS
There were 17 RCTs of licensed drugs versus placebo in IBS with constipation (4603 patients placebo) and 17 trials in IBS with diarrhea (3908 patients placebo). In IBS with constipation, according to FDA criteria, pooled composite, abdominal pain, and stool response rates with placebo over ≥6 of 12 weeks were 18.9%, 34.6%, and 30.1%, respectively. Evaluating response rates over ≥9 of 12 weeks led to placebo response rates of 4.3% for the composite endpoint, 24.5% for abdominal pain, and 7.7% for stool. In IBS with diarrhea, pooled placebo response rates according to FDA criteria were 16.2% for the composite endpoint, 40.2% for abdominal pain, and 16.2% for stool. Increasing the threshold used to define abdominal pain response from ≥30% improvement to ≥40% or ≥50% led to lower placebo response rates of 34.5% and 23.4%.
CONCLUSIONS
Future RCTs should adhere to current FDA-recommended endpoints for IBS because these lead to lower placebo response rates. However, consideration should be given to further refining some of these to better differentiate between active drug and placebo.
Topics: Abdominal Pain; Adult; Constipation; Diarrhea; Humans; Irritable Bowel Syndrome; Pharmaceutical Preparations; Placebo Effect; Treatment Outcome
PubMed: 34425274
DOI: 10.1016/j.cgh.2021.08.025 -
Journal of the American College of... Dec 2022The objective of this study was to conduct a systematic review and meta-analysis of the diagnostic accuracy of the clinical signs, symptoms, laboratory investigations,...
STUDY OBJECTIVE
The objective of this study was to conduct a systematic review and meta-analysis of the diagnostic accuracy of the clinical signs, symptoms, laboratory investigations, and imaging modalities commonly used in patients with clinically suspected renal colic.
METHODS
We conducted this systematic review and meta-analysis according to an a priori, registered protocol (PROSPERO CRD42017055153). A literature search was performed using MEDLINE and EMBASE from inception to July 2, 2020. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2, calculated likelihood ratios (LRs), and applied a random-effects model for meta-analysis.
RESULTS
Among 7641 references screened, 76 were included in the systematic review and 53 were included in the meta-analyis. The overall pooled prevalence for ureteral stones was 63% (95% confidence interval [CI], 58%-67%). No individual demographic feature, symptom, or sign when present had an LR+ ≥2.0 for identifying ureterolithiasis. A (Sex, Timing and Origin of pain, race, presence or absence of Nausea, and Erythrocytes) STONE score ≥10 increased (sensitivity 0.49, specificity 0.91, LR 5.3 [95% CI, 4.1-6.7]) and a STONE score <6 reduced the likelihood of ureteral stones (sensitivity 0.94, specificity 0.43, LR 0.15 [95% CI, 0.10-0.22]). Standard-dose (sensitivity 0.96, specificity 0.94, LR+ 16 [95% CI, 11-23], LR- 0.05 [95% CI, 0.03-0.07]) and low-dose computed tomography (CT) scanning (sensitivity 0.93, specificity 0.94, LR+ 17 [95% CI, 8.8-31], LR- 0.08 [95% CI, 0.03-0.19]) were the most useful imaging techniques for identifying patients with or without ureteral stones.
CONCLUSIONS
Individual signs, symptoms, or the presence of microscopic hematuria do not substantially impact the likelihood of ureteral stones in patients with clinically suspected renal colic. The STONE score at high and low thresholds and a modified STONE score at a high threshold may sufficiently guide physicians' decisions to obtain imaging. Low-dose, non-contrast CT imaging provides superior diagnostic accuracy compared with all other imaging index tests that are comparable with standard CT imaging. Limitations of the evidence include methodological shortcomings and considerable heterogeneity of the included studies.
PubMed: 36474707
DOI: 10.1002/emp2.12831 -
The Journal of Pain Dec 2016Although clinical studies suggest depressed patients may be more vulnerable to pain, experimental research is equivocal. This meta-analysis aimed to clarify whether... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Although clinical studies suggest depressed patients may be more vulnerable to pain, experimental research is equivocal. This meta-analysis aimed to clarify whether depression is associated with altered pain perception in response to noxious stimulation and to identify factors that might influence this association. A search of major electronic databases was conducted to identify experimental studies investigating pain response in depressed participants versus healthy control participants using established pain outcome measures. Random effects meta-analysis of standardized mean differences was conducted on data from 32 studies (N = 1,317). For high-intensity noxious stimulation, overall pain tolerance was similar across depressed and control groups (Hedges g = .09, P = .71, studies = 10). For low-intensity stimulation, a small, but statistically significant higher mean sensory threshold (g = .35, P = .01, studies = 9) and pain threshold (g = .32, P = .02, studies = 25) was observed in depressed participants, suggesting diminished pain. However, considerable heterogeneity in the direction and magnitude of effects was observed, indicating a likely condition-specific effect of depression on pain. Subgroup analysis found that pain threshold/tolerance was increased in depression for exteroceptive (cutaneous) stimulation but decreased for interoceptive (ischemic) stimulation, but that substantial heterogeneity remained. Overall, results provide some support for altered pain processing in depression, but suggest this link is dependent upon modality and additional, unidentified factors.
PERSPECTIVE
This meta-analysis of experimental studies suggests potential effects of depression on pain perception are variable and likely to depend upon multiple factors. The contrasting pattern for ischemic versus other noxious stimuli suggests that stimulus modality is a key factor, which could help explain discrepancies across clinical and experimental findings.
Topics: Depression; Humans; Pain Perception; Pain Threshold
PubMed: 27589910
DOI: 10.1016/j.jpain.2016.08.007 -
BMC Musculoskeletal Disorders Feb 2022Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may...
BACKGROUND
Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may improve pain sensitisation, the amount and type of exercise remains unclear. This systematic review examines the evidence for an effect of aerobic exercise on pain sensitisation in musculoskeletal conditions.
METHODS
Systematic searches of six electronic databases were conducted. Studies were included if they examined the relationship between aerobic physical activity and pain sensitisation in individuals with chronic musculoskeletal pain, but excluding specific patient subgroups such as fibromyalgia. Risk of bias was assessed using Cochrane methods and a qualitative analysis was conducted.
RESULTS
Eleven studies (seven repeated measures studies and four clinical trials) of 590 participants were included. Eight studies had low to moderate risk of bias. All 11 studies found that aerobic exercise increased pressure pain thresholds or decreased pain ratings in those with musculoskeletal pain [median (minimum, maximum) improvement in pain sensitisation: 10.6% (2.2%, 24.1%)]. In these studies, the aerobic exercise involved walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4-60 min duration. Improvement in pain sensitisation occurred after one session in the observational studies and after 2-12 weeks in the clinical trials.
CONCLUSIONS
These findings provide evidence that aerobic exercise reduces pain sensitisation in individuals with musculoskeletal pain. Further work is needed to determine whether this translates to improved patient outcomes, including reduced disability and greater quality of life.
Topics: Exercise; Exercise Therapy; Fibromyalgia; Humans; Musculoskeletal Pain; Quality of Life
PubMed: 35114987
DOI: 10.1186/s12891-022-05047-9 -
Evidence-based Complementary and... 2015Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the... (Review)
Review
Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the efficacy of acupuncture therapy in sciatica are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for sciatica. Methods. Comprehensive searches of 8 databases were conducted up until April 2015. Outcomes included effectiveness (proportion of patients who improved totally or partly in clinical symptoms), pain intensity, and pain threshold. Effect sizes were presented as risk ratio (RR) and mean difference (MD). Pooled effect sizes were calculated by fixed effects or random effects model. Results. A total of 12 studies (involving 1842 participants) were included. Results showed that acupuncture was more effective than conventional Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16-1.25), pain intensity (MD -1.25, 95% CI: -1.63 to -0.86), and pain threshold (MD: 1.08, 95% CI: 0.98-1.17). Subgroup and sensitivity analysis found that the results did not change in different treatment method and drug categories substantially. The reported adverse effects were acceptable. Conclusions. Acupuncture may be effective in treating the pain associated with sciatica.
PubMed: 26425130
DOI: 10.1155/2015/192808 -
Frontiers in Integrative Neuroscience 2022To evaluate the evidence for altered cortical and spinal cord functions in individuals with patellofemoral pain (PFP).
OBJECTIVE
To evaluate the evidence for altered cortical and spinal cord functions in individuals with patellofemoral pain (PFP).
METHODS
We conducted a comprehensive search of databases to appraise and analyze the studies published prior to December 10, 2021 that examined spinal reflex excitability measured using Hoffmann reflex (H-reflex) amplitudes, corticospinal excitability measured using transcranial magnetic stimulation (TMS)-elicited motor evoked potential (MEP) amplitudes, motor threshold (MT), or stimulus-response (SR) curves, cortical reorganization assessed using TMS cortical mapping or structural magnetic resonance imaging (MRI), or functional changes of the brain assessed using functional MRI (fMRI) in individuals with PFP.
RESULTS
Eight studies were eligible for analyses. While an earlier study showed that pain had no effect on the H-reflex amplitude of the quadriceps muscle, more recent evidence reported a decrease in vastus medialis (VM) H-reflex amplitude in participants with PFP. VM H-reflex amplitude was correlated with pain, chronicity, physical function, and isometric knee extensor torque production in participants with PFP. Altered corticospinal excitability was reported in participants with PFP, observed as increased MT in the VM and vastus lateralis (VL) muscles. In addition, cortical reorganization has been observed, where decreased number of cortical peaks, shifts and reduced volumes, and increased overlap of motor cortex representations for the VM, VL, and rectus femoris (RF) muscles were reported in participants with PFP.
CONCLUSION
There is emerging evidence on altered cortical and spinal cord functions in individuals with PFP, however, solid conclusions cannot be drawn due to limited literature available. Further research is needed to better understand the adaptations of the brain and spinal cord in this population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42020212128.
PubMed: 35197832
DOI: 10.3389/fnint.2022.791719 -
Health Technology Assessment... Jul 2023Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease.
BACKGROUND
Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease.
OBJECTIVES
The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing.
DATA SOURCES
The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment.
METHODS
A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results.
RESULTS
The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters.
LIMITATIONS
Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited.
CONCLUSIONS
Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021286891.
FUNDING
Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.
Topics: Humans; Cost-Benefit Analysis; Liver Cirrhosis; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; State Medicine
PubMed: 37839810
DOI: 10.3310/KGJU3398 -
Pain Sep 2019Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an... (Meta-Analysis)
Meta-Analysis Review
Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability, and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Of the 37 eligible studies (n = 3860 participants), 32 were prospective cohort studies and 5 randomised controlled trials. Pain was an outcome in 30 studies, disability in 11, and negative affect in 3. Meta-analysis revealed that baseline QST predicted musculoskeletal pain (mean r = 0.31, 95% confidence interval [CI]: 0.23-0.38, n = 1057 participants) and disability (mean r = 0.30, 95% CI: 0.19-0.40, n = 290 participants). Baseline modalities quantifying central mechanisms such as temporal summation and conditioned pain modulation were associated with follow-up pain (temporal summation: mean r = 0.37, 95% CI: 0.17-0.54; conditioned pain modulation: mean r = 0.36, 95% CI: 0.20-0.50), whereas baseline mechanical threshold modalities were predictive of follow-up disability (mean r = 0.25, 95% CI: 0.03-0.45). Quantitative sensory testing indices of pain hypersensitivity might help develop targeted interventions aiming to improve outcomes across a range of musculoskeletal conditions.
Topics: Affect; Disabled Persons; Humans; Musculoskeletal Pain; Pain Measurement; Pain Threshold; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 31045746
DOI: 10.1097/j.pain.0000000000001590 -
PloS One 2014The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system.
METHODS
Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed.
RESULTS
Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception.
CONCLUSIONS
Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.
Topics: Acupuncture Therapy; Databases, Bibliographic; Humans; Pain Threshold
PubMed: 25502787
DOI: 10.1371/journal.pone.0113731 -
Vaccines Jan 2023Comprehensive safety and efficacy studies of COVID-19 vaccines might reduce the apprehension of the general population about the adverse reactions and duration of... (Review)
Review
Comprehensive safety and efficacy studies of COVID-19 vaccines might reduce the apprehension of the general population about the adverse reactions and duration of protection offered by them. The study aimed to conduct a systemic review on the four COVID-19 vaccines (AstraZeneca, Pfizer, Moderna, and Janssen) approved in Saudi Arabia. The study was conducted by reviewing the published articles from electronic databases such as PubMed, Embase, Cochrane Library and Web of Science using the search terms "COVID-19", "Vaccine", "Safety", "Efficacy" and "Human trials" and as per the standard guidelines for systemic review. The review analyzed eighteen articles and the data from them were evaluated to analyze the safety and efficacy of the vaccines in different groups of population such as males, females, those above 18 years and people with co-morbidities. The common local reactions observed after vaccination were pain at the site of injection (40-70%), redness (16-30%), swelling (18-39%) and tenderness (20-40%). The systemic reactions reported were fever (40-60%), chills (12-23%), fatigue (44-65%), headache (30-42%) and muscle pain (15-40%). The efficacy was observed to be above the threshold value (60%) stipulated by the WHO. However, precautions need to be followed while vaccinating special groups of population such as those that are pregnant, lactating or experiencing severe illness. Additionally, the rare and serious adverse events reported remotely after vaccination need more studies.
PubMed: 36851158
DOI: 10.3390/vaccines11020281