-
Neurogastroenterology and Motility Jun 2022Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome (IBS). Therefore, we conducted a systematic review and meta-analysis to assess the proportion of patients randomized to placebo or active drug experiencing any adverse event in trials of licensed drugs for IBS with constipation (IBS-C) or diarrhea (IBS-D), and to estimate the risk of developing adverse events among patients randomized to placebo.
METHODS
We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through June 2021) to identify RCTs comparing licensed drugs with placebo in adults with IBS-C or IBS-D. We generated Forest plots of pooled adverse event rates in both active drug and placebo arms and pooled risk differences (RDs) with 95% confidence intervals (CIs).
KEY RESULTS
There were 21 RCTs of licensed drugs versus placebo in IBS-C (5953 patients placebo) and 17 in IBS-D (3854 patients placebo). Overall, 34.9% and 46.9% of placebo patients in IBS-C and IBS-D trials, respectively, developed at least one adverse event, with a statistically significantly higher risk of any adverse event and withdrawal due to an adverse event with active drug. In IBS-C and IBS-D trials, rates of each individual adverse event were generally higher with active drug. However, in IBS-C trials, only diarrhea or headache was significantly more common with active drug (RD 0.066 (95% CI 0.043-0.088) and RD 0.011 (95% CI 0.002-0.021), respectively), and in IBS-D trials only constipation, nausea, or abdominal pain (RD 0.096 (95% CI 0.054-0.138), 0.014 (95% CI 0.002-0.027), and 0.018 (95% CI 0.002-0.034), respectively).
CONCLUSIONS & INFERENCES
Patients with IBS randomized to placebo have a high risk of reporting adverse events, which might relate to both nocebo and non-nocebo factors. Although patients' expectations and psychosocial factors may be involved, further understanding of the mechanisms are important to control or optimize these effects in RCTs, as well as in clinical practice.
Topics: Abdominal Pain; Adult; Constipation; Craniosynostoses; Diarrhea; Humans; Intellectual Disability; Irritable Bowel Syndrome; Nocebo Effect; Randomized Controlled Trials as Topic
PubMed: 34672052
DOI: 10.1111/nmo.14279 -
The Journal of Craniofacial SurgeryCraniosynostosis can be associated with raised intracranial pressure (ICP), which can pose deleterious effects on the brain and vision if untreated. Estimating ICP in...
OBJECTIVE
Craniosynostosis can be associated with raised intracranial pressure (ICP), which can pose deleterious effects on the brain and vision if untreated. Estimating ICP in children is challenging, whilst gold standard direct intracranial measurement of ICP is invasive and carries risk. This systematic review aims to evaluate the role of optical coherence tomography (OCT), a noninvasive imaging technique, for detecting raised ICP in children with craniosynostosis.
METHODS
The authors conducted a systematic review of the literature published from inception until 19 August, 2019 in the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, and EMBASE. Eligible studies evaluated the role of OCT in detecting raised ICP in children aged 0 to 16 years with craniosynostosis. Main outcome measures were sensitivity and specificity of OCT parameters for raised ICP. Quality assessment was performed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies.
RESULTS
Out of 318 records identified, data meeting the inclusion criteria were obtained from 3 studies. The quality of 2 studies was poor whilst 1 was fair. Optical coherence tomography demonstrated higher sensitivity and specificity for detecting raised ICP compared to fundus examination, clinical history, radiological testing, and visual field testing.
CONCLUSIONS
This systematic review demonstrated a lack of quality evidence for OCT as a screening tool for children with craniosynostosis. Further research is required to clarify the strength of OCT in this role and to determine which OCT parameters are most appropriate.
Topics: Child; Craniosynostoses; Cross-Sectional Studies; Humans; Intracranial Hypertension; Intracranial Pressure; Tomography, Optical Coherence
PubMed: 33185414
DOI: 10.1097/SCS.0000000000006771 -
Foot and Ankle Surgery : Official... Oct 2022The primary aim was to determine the clinical success rate after treatment for talocalcaneal (TCC) and calcaneonavicular coalitions (CNC). The secondary aim was to...
BACKGROUND
The primary aim was to determine the clinical success rate after treatment for talocalcaneal (TCC) and calcaneonavicular coalitions (CNC). The secondary aim was to evaluate the complication, recurrence and revision rate.
METHODS
A search was carried out in MEDLINE, EMBASE and Cochrane Library. Methodological quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS) criteria. The primary outcome was the clinical success rate and was pooled per type of coalition and treatment modality. 95% Confidence Intervals (CI) of the success rates were calculated. Secondary outcomes included complication rates, coalition recurrence rates, revision rates and pain improvement using the Visual Analogue Scale (VAS). A sub-analysis on interposition material was performed.
RESULTS
43 articles comprising of 1284 coalitions were included, with a pooled mean follow-up of 51 months. Methodological quality was fair. The overall pooled success rate for TCCs was 79% (95% CI, 75%-83%). Conservative treatment, open resection and arthroscopic resection of TCCs resulted in success rates of 58% (95% CI, 42%-73%), 80% (95% CI, 76%-84%) and 86% (95% CI, 71%-94%), respectively. CNCs have an overall success rate of 81% (95% CI, 75%-85%), with 100% (95% CI, 34%-100%), 80% (95% CI, 74%-85%) and 100% (95% CI, 65%-100%) for conservative treatment, open resection and arthroscopic resection, respectively. Pooled complication rates of 4% (95% CI, 3%-7%) for TCCs and 6% (95% CI, 4%-11%) for CNCs were found. The success rates of resection with and without interposition material for TCCs were 83% (95% CI, 78%-87%) and 79% (95% CI, 65%-88%), and for CNCs 81% (95% CI, 76%-86%) and 69% (95% CI, 44%-85%), respectively.
CONCLUSION
Treatment of tarsal coalitions can be considered good to excellent as well as safe, with an overall clinical success rate of 79% for TCCs and 81% for CNCs. Arthroscopic resection of the coalition appears to be non-inferior to open resection of TCCs and CNCs.
LEVEL OF EVIDENCE
Level IV, Systematic Review.
Topics: Carpal Bones; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Stapes; Synostosis; Tarsal Bones; Tarsal Coalition
PubMed: 35397990
DOI: 10.1016/j.fas.2022.03.011 -
Neuro-Chirurgie Nov 2019Craniosysnostosis surgical corrections are routine procedures in the pediatric neurosurgical field. However, these procedures result in significant blood loss....
INTRODUCTION
Craniosysnostosis surgical corrections are routine procedures in the pediatric neurosurgical field. However, these procedures result in significant blood loss. Tranexamic acid (TXA) is an antifibrinolytic drug, which has demonstrated a significant reduction in perioperative blood loss in many pediatric surgical procedures such as cardiac surgery and scoliosis surgery. We conducted a systematic review to evaluate protocols of TXA use in pediatric craniosynostosis procedures and its effect on intraoperative blood loss and transfusions.
MATERIAL AND METHODS
A comprehensive literature review of the National Library of Medicine (PubMed) database was performed to identify relevant studies. We included any clinical study reporting on blood loss or blood transfusion for pediatric craniosynostosis surgery with intraoperative use of tranexamic acid, with the following limits: publication date from inception to May 2019; reports in English.
RESULTS
Thirteen studies were eligible for our review. Of the 13 studies, 4 were prospective, randomised, double-blind controlled trials, 9 were retrospective studies, tailored as a "before-after" studies, comparing blood loss and transfusion without/with TXA. TXA significantly decreases the number and volume of packed red blood cell transfusions and the rate of transfusion in children undergoing craniosynostosis surgery. Significantly fewer fresh frozen plasma transfusions were required in the TXA groups in 2 randomised studies. Length of stay in hospital was significantly lower with the use of TXA in three studies. Advantages of TXA administration also include an excellent patient tolerance of side effects, ease of administration and low cost.
CONCLUSION
TXA significantly reduces blood loss and the need for transfusions in children undergoing craniosynostosis surgery. TXA administration should be a routine part of strategy to reduce blood loss and limit transfusions in these procedures.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Child; Child, Preschool; Craniosynostoses; Humans; Infant; Plastic Surgery Procedures; Tranexamic Acid
PubMed: 31586574
DOI: 10.1016/j.neuchi.2019.09.020 -
Genes Feb 2023Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant...
Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant in one of just seven genes or have a chromosomal abnormality, over 60 genes are known to be recurrently mutated, thus comprising a long tail of rarer diagnoses. Genome sequencing for the diagnosis of rare diseases is increasingly used in clinical settings, but analysis of the data is labor intensive and involves a trade-off between achieving high sensitivity or high precision. PanelApp, a crowd-sourced disease-focused set of gene panels, was designed to enable prioritization of variants in known disease genes for a given pathology, allowing enhanced identification of true-positives. For heterogeneous disorders like craniosynostosis, these panels must be regularly updated to ensure that diagnoses are not being missed. We provide a systematic review of genetic literature on craniosynostosis over the last 5 years, including additional results from resequencing a 42-gene panel in 617 affected individuals. We identify 16 genes (representing a 25% uplift) that should be added to the list of bona fide craniosynostosis disease genes and discuss the insights that these new genes provide into pathophysiological mechanisms of craniosynostosis.
Topics: Child; Humans; Craniosynostoses; Cranial Sutures
PubMed: 36980886
DOI: 10.3390/genes14030615 -
American Journal of Medical Genetics.... Aug 201822q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety disorders, psychotic disorders, and other psychiatric conditions. In the general...
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety disorders, psychotic disorders, and other psychiatric conditions. In the general population, psychiatric disorders are treated with proven pharmacological and non-pharmacological therapies, such as cognitive behavioral therapy (CBT). To begin to assess the feasibility and efficacy of non-pharmacological therapies in 22q11.2DS, we performed a systematic search to identify literature on non-pharmacological interventions for psychiatric disorders in individuals with 22q11.2DS. Of 1,240 individual publications up to mid-2016 initially identified, 11 met inclusion criteria. There were five literature reviews, five publications reporting original research (two originating from a single study), and one publication not fitting either category that suggested adaptations to an intervention without providing scientific evidence. None of the original research involved direct study of the evidence-based non-pharmacological therapies available for psychiatric disorders. Rather, these four studies involved computer-based or group interventions aimed at improving neuropsychological deficits that may be associated with psychiatric disorders. Although the sample sizes were relatively small (maximum 28 participants in the intervention group), these reports documented the promising feasibility of these interventions, and improvements in domains of neuropsychological functioning, including working memory, attention, and social cognition. The results of this review underline the need for research into the feasibility and efficacy of non-pharmacological treatments of psychiatric disorders in individuals with 22q11.2DS to inform clinical care, using larger samples, and optimally, standard randomized, placebo-controlled, clinical trials methodology.
Topics: Adult; Arachnodactyly; Cognitive Behavioral Therapy; Craniosynostoses; DiGeorge Syndrome; Female; Humans; Male; Marfan Syndrome; Psychotic Disorders
PubMed: 29363845
DOI: 10.1002/ajmg.a.38612